ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve Through Implantation of ACURATE in Subjects InDicatEd for TAVR
Phase: NA
Conditions: Aortic Stenosis
Sponsor: Boston Scientific Corporation

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve 
through Implantation of ACURATE in Subjects InDicatEd for TAVR 
 
 
ACURATE IDE 
S2408 
CLINICAL INVESTIGATION PLAN 
National Clinical Trial Identification Number: NCT03735667 
 
 
 
Sponsor: 
Boston Scientific Corporation  
300 Boston Scientific Way 
Marlborough, MA 01752 USA 
European Authorized Representative 
Boston Scientific International S.A. 
Le Val Saint-Quentin 
2 rue René Caudron, 78960 
Voisins le Bretonneux, France 
Australian Representative 
Boston Scientific Pty. Ltd. 
Building 1, Level 6 
191 O’Riordan Street 
Mascot, NSW 2020, Australia 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should 
be held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
Lisa Currier 
Senior Clinical Trial Manager, Interventional Cardiology 
Boston Scientific Corporation 
100 Boston Scientific Way, Marlborough, MA  01752 USA 
Beth Louh 
Senior Clinical Trial Manager, Interventional Cardiology 
Boston Scientific Corporation 
100 Boston Scientific Way, Marlborough, MA  01752 USA 
Sarah Zanon 
Director, Clinical Trials, Interventional Cardiology – Structural Heart  
Boston Scientific Corporation 
Ritterquai 8  
4500 Solothurn, Switzerland 
Coordinating Principal 
Investigators 
Interventional Cardiologist Study Co-Principal Investigator 
Raj R. Makkar, MD 
Department of Interventional Cardiology 
Cedars-Sinai Heart Institute  
8700 Beverly Boulevard, Los Angeles, CA 90048 USA 
Cardiac Surgeon Study Co-Principal Investigator 
Michael J. Reardon, MD 
Methodist DeBakey Heart & Vascular Center  
6550 Fannin Street, Suite 1401, Houston, TX 77030 USA 
Original Release: 12-Oct-2018 
Current Version: 20-Jan-2023 
Revision History 
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12-Oct-2018 
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10-Jan-2019 
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C* 
21-May-2019 
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08-Jan-2020 
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*Boston Scientific Corporation internal update only; Versions A, C, E, F, and G were not implemented or distributed to 
clinical centers. 

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2. Protocol Synopsis 
ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
Study 
Objective(s) 
To evaluate safety and effectiveness of the ACURATE Transfemoral 
Aortic Valve System for transcatheter aortic valve replacement (TAVR) 
in subjects with severe native aortic stenosis who are indicated for 
TAVR. 
Planned 
Indication(s) for 
Use  
The ACURATE Transfemoral Aortic Valve System is intended to 
improve aortic valve function in subjects with severe native aortic 
stenosis who are indicated for TAVR. 
Test Device and 
Sizes 
ACURATE Transfemoral Aortic Valve System (ACURATE) 
Device Name/Size 
Description 
ACURATE neo2™ Aortic Valve 
Valve size: 
 - S (small) 
 - M (medium) 
 - L (large) 
with 23mm, 25mm, and 27mm 
nominal diameter at waist level, 
respectively 
Includes 3 main components: 
- A three-leaflet porcine pericardial 
bioprosthetic aortic valve; 
- A self-expandable Nitinol stent; 
- A double porcine pericardium skirt 
sutured on the inner and outer surface 
of the stent to prevent paravalvular 
leaks.  
Introduced via the iliofemoral artery. 
ACURATE neo2™ 
Transfemoral Delivery System 
The delivery system is 
compatible with the S, M, and L 
valve sizes. 
Allows positioning and delivery of the 
transcatheter valve via iliofemoral 
access. 
ACURATE Prime™ Aortic 
Valve XL* 
Valve size: 
 - XL (extra-large) 
with 29mm nominal diameter at 
waist level 
Includes 3 main components: 
-  A three-leaflet porcine pericardial 
bioprosthetic aortic valve. 
-  A self-expandable Nitinol stent. 
-  A double porcine pericardium skirt 
sutured on the inner and outer 
surface of the stent to prevent 
paravalvular leaks.  
Introduced via the iliofemoral artery. 
ACURATE Prime™ 
Transfemoral Delivery System 
XL* 
Allows positioning and delivery of the 
transcatheter XL valve via iliofemoral 
access. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
ACURATE Prime™ Loading 
Kit XL* 
Allows loading of the XL valve onto the 
delivery system.  
* ACURATE Prime XL is only available in the United States. 
Control Device 
and Sizes 
In the Main Randomized Cohort and in the Extended Durability Study 
(see study cohorts described below), subjects assigned to the control arm 
will receive a commercially available balloon-expandable SAPIEN 3™ 
Transcatheter Heart Valve or future iteration (SAPIEN 3; Edwards 
Lifesciences LLC, Irvine, CA, USA) or a commercially available self-
expanding CoreValve® Transcatheter Aortic Valve Replacement 
System, CoreValve® Evolut™ R Recapturable TAVR System, 
EVOLUT™ PRO System, or future iteration (CoreValve; Medtronic, 
Inc., Dublin, Ireland) TAVR device that is introduced via the femoral 
artery using conventional catheterization techniques.  
Note 1: Every subject in the Main Randomized Cohort and the 
Extended Durability Study must be deemed treatable with an available 
size of both the test (ACURATE) device and the control device. 
Study Design 
ACURATE IDE is a prospective, multicenter trial designed to evaluate 
the safety and effectiveness of the ACURATE Transfemoral Aortic 
Valve System for TAVR in subjects who have severe native aortic 
stenosis and are indicated for TAVR. Study cohorts include the 
following: 
• Main Randomized Cohort: A prospective, multicenter, 1:1 
randomized controlled trial (RCT; ACURATE versus Control 
[commercially available SAPIEN 3 or CoreValve] TAVR device). 
Randomization will be stratified by center and by intended control 
device. 
• Roll-In Cohort: A non-randomized Roll-In phase with the test 
device. Centers that do not have implantation experience with the 
ACURATE neo™ Aortic Bioprosthesis (transfemoral delivery; 
Boston Scientific Corporation, Marlborough, MA, USA) will 
perform at least 2 Roll-In cases with ACURATE neo2 before 
commencing treatment in the randomized cohort. Centers with 
prior experience with ACURATE are not required to do Roll-In 
cases. Data from Roll-In subjects will be summarized separately 
from the randomized cohort and will not be included in the primary 
endpoint analysis. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
• 4D CT Imaging Substudy: Selected centers with the ability to 
perform high quality 4D computed tomography (CT) scans will 
include subjects from the Main Randomized Cohort in a 4D CT 
Imaging Substudy to assess the prevalence of reduced leaflet 
mobility and hypoattenuated leaflet thickening (HALT) and the 
relationship, if any, to clinical events. Subjects will be randomized 
to test (ACURATE) and control device. 
• ACURATE Prime™ XL Nested Registry: A non-randomized, 
nested registry cohort of subjects who will receive the ACURATE 
Prime™ Transfemoral Aortic Valve System XL (ACURATE 
Prime XL Nested Registry). Participating centers will be a subset 
of United States centers that have enrolled subjects in ACURATE 
IDE. Data from subjects in this nested registry will be summarized 
separately from the other cohorts. 
• ACURATE Extended Durability Study: An additional 1:1 
randomized study (ACURATE versus Control [commercially 
available SAPIEN 3 or CoreValve] TAVR device) including only 
subjects considered to be at low surgical risk. Subjects will receive 
ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime 
XL. Randomization will be stratified by center and by intended 
control device. Low-risk subjects receiving ACURATE neo2 will 
be enrolled in the Extended Durability Study only after enrollment 
of the Main Randomized Cohort is completed. Enrollment of low-
risk subjects with ACURATE Prime XL will start after enrollment 
in both the Main Randomized Cohort and the ACURATE Prime 
XL Nested Registry is completed. Data from subjects in the 
Extended Durability Study will be summarized separately from 
other cohorts. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in the ACURATE Extended 
Durability Study. 
• ACURATE Continued Access Study (CAS): An additional 
cohort of subjects receiving ACURATE neo2 (S, M, and L valve 
sizes) or ACURATE Prime XL. Enrollment of subjects with 
ACURATE neo2 will start after enrollment of the ACURATE IDE 
Main Randomized Cohort is completed. Enrollment of subjects 
with ACURATE Prime XL will start after enrollment in both the 
Main Randomized Cohort and the ACURATE Prime XL Nested 
Registry is completed. Subjects at all surgical risks may be 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
enrolled in ACURATE CAS, but low-risk subjects will be 
considered for enrollment only after enrollment in the Extended 
Durability Study is completed. Data from subjects in the 
ACURATE CAS will be summarized separately from other cohorts 
and will be used to further assess performance and safety. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE CAS. 
The devices and risk levels for the ACURATE IDE cohorts are 
summarized in the table below. 
Devices and Risk Levels for ACURATE IDE Cohorts 
Device 
Cohort 
Roll-In 
Main 
RCT 
Prime XL 
Nested 
Registry 
Extended 
Durability1 
Continued 
Access 
Study1 
ACURATE neo2 
(S, M, L) 
All risks 
All risks 
N/A 
Low risk 
All risks2 
ACURATE Prime 
(XL) 
N/A 
N/A 
All risks 
Low risk3 
All risks2,3 
Note 1: Enrollment of subjects in the Extended Durability cohort and the CAS 
cohort will begin after completion of enrollment in the Main RCT. 
Note 2: Enrollment of low-surgical-risk subjects in the CAS cohort will begin after 
completion of enrollment the Extended Durability cohort. 
Note 3: Enrollment of subjects receiving ACURATE Prime XL in the Extended 
Durability and CAS cohorts will begin after enrollment completion in both the Main 
RCT and Prime XL Nested Registry. 
Abbreviations: CAS=Continued Access Study; N/A=not applicable; 
RCT=randomized controlled trial 
 
The ACURATE IDE study will be conducted in accordance with 
21 CFR Parts 11, 50, and 54; the relevant parts of the International 
Conference on Harmonisation (ICH) Guidelines for Good Clinical 
Practices (GCP); the International Standard ISO 14155 Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical 
Practice; ethical principles that have their origins in the Declaration of 
Helsinki; and pertinent individual country/state/local laws and 
regulations. The study shall not begin until the required 
approval/favorable opinion from the Institutional Review 
Board/Research Ethics Board/Human Research Ethics Committee/ 
Independent Ethics Committee (IRB/REB/HREC/IEC) and/or 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
regulatory authority has been obtained, if appropriate. The study design 
is summarized in the figure below. 
  
ACURATE IDE Study Design Overview 
Planned 
Number of 
Subjects and 
Planned 
Number of 
Investigational 
Centers/ 
Countries 
Subjects will be enrolled at up to 85 centers in the United States, 
Canada, Australia, and Europe. In total, there will be up to 2820 subjects 
enrolled in ACURATE IDE across the various cohorts. It is expected 
that >80% of enrolled subjects will be from the United States. The 
number of subjects intended for each cohort is shown in the table below. 
To achieve sufficient distribution of lower risk subjects in the Main 
Randomized Cohort, there will be ≥ 30% intermediate-risk randomized 
subjects and ≥ 35% low-risk randomized subjects enrolled. The 
ACURATE Prime XL Nested Registry and the ACURATE Continued 
Access Study will enroll subjects at all surgical risks. Only low-risk 
subjects will be enrolled in the ACURATE Extended Durability Cohort. 
Cohort 
Number of Subjects 
Main Randomized Cohort 
1500* 
Roll-In Cohort 
Up to 170 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
ACURATE Prime XL Nested Registry 
50‡ 
ACURATE Extended Durability Study 
A minimum of 100† 
ACURATE Continued Access Study (CAS) 
Up to 1000§ 
*  A subset of subjects (minimum of 200) in the Main Randomized Cohort 
will also be enrolled in the 4D CT Imaging Substudy. 
‡  Subjects will be enrolled at up to 20 centers in the United States. 
† Only low-risk subjects will be included in the Extended Durability Study. 
§ Low-risk subjects will be considered for enrollment in ACURATE CAS 
after enrollment is completed in the Extended Durability Study. 
  
Primary 
Endpoint 
Composite of all-cause mortality, all stroke, and rehospitalization† at 1 
year. 
† Hospitalization for valve-related symptoms or worsening congestive 
heart failure (NYHA class III or IV); per VARC-2 definition  
Additional 
Measurements 
This section describes required assessments to be performed in the 
ACURATE IDE study. 
Additional measurements based on the VARCa endpoints and definitions 
will be collected peri- and post-procedure, at discharge or 7 days post-
procedure (whichever comes first), 30 days, 6 months, and annually 
through 10 years post index procedure, unless otherwise specified 
below.  
• Safety endpoints adjudicated by an independent Clinical Events 
Committee (CEC): 
- Mortality: all-cause, cardiovascular, and non-cardiovascular 
- Stroke: disabling and non-disabling 
- Myocardial infarction (MI): periprocedural (≤72 hours post index 
procedure) and spontaneous (>72 hours post index procedure) 
- Bleeding: life-threatening (or disabling) and major (through 5 
years) 
- Acute kidney injury (≤7 days post index procedure): based on the 
AKIN System Stage 3 (including renal replacement therapy) or 
Stage 2 
- Major vascular complication (through 5 years) 
- Repeat procedure for valve-related dysfunction (surgical or 
interventional therapy) 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
- Hospitalization for valve-related symptoms or worsening 
congestive heart failure (NYHA class III or IV) 
- New permanent pacemaker implantation resulting from new or 
worsened conduction disturbances  
- New onset of atrial fibrillation or atrial flutter  
- Coronary obstruction: periprocedural (≤72 hours post index 
procedure) 
- Ventricular septal perforation: periprocedural (≤72 hours post 
index procedure) 
- Mitral apparatus damage: periprocedural (≤72 hours post index 
procedure) 
- Cardiac tamponade: periprocedural (≤72 hours post index 
procedure) 
- Valve migration 
- Valve embolization 
- Ectopic valve deployment 
- Transcatheter aortic valve (TAV)-in-TAV deployment 
- Prosthetic aortic valve thrombosis 
- Prosthetic aortic valve endocarditis 
• Device performance endpoints peri- and post-procedure:  
- Successful vascular access, delivery and deployment of the study 
valve, and successful retrieval of the delivery system 
- Grade of aortic valve regurgitation: paravalvular, central, and 
combined 
• Device success, assessed at procedure and defined as absence of 
procedural mortality, correct positioning of a single valve into the 
proper anatomical location, and intended performance of the study 
device (indexed effective orifice area [iEOA] >0.85 cm2/m2 for 
BMI <30 kg/m2 and iEOA >0.70 cm2/m2 for BMI ≥30 kg/m2 plus 
either a mean aortic valve gradient <20 mmHg or a peak velocity 
<3m/sec, and no moderate or severe prosthetic valve aortic 
regurgitation) 
• Additional indications of prosthetic aortic valve performance as 
measured by transthoracic echocardiography (TTE; see Note 2 and 
Note 3 below) and assessed by an independent core laboratory, 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
including EOA, mean and peak aortic gradients, peak aortic 
velocity, and grade of aortic regurgitation 
• Functional status as evaluated by New York Heart Association 
(NYHA) classification (see Note 3 below) 
• Neurological status (see Note 4 below) as determined by the 
following: 
- National Institutes of Health Stroke Scale (NIHSS) conducted by 
a neurology professional or certified personnel at discharge and 
1 year  
- Modified Rankin Scale (mRS) conducted by a neurology 
professional or certified personnel at discharge and all follow-up 
visits (see Note 4 below) 
- Neurological physical exam conducted by a neurologist, 
neurology fellow, neurology physician assistant, or neurology 
nurse practitioner in all subjects where stroke is suspected  
• Health status as evaluated by Kansas City Cardiomyopathy and 
SF-12 Quality of Life questionnaires at baseline, 1 month, and 1 and 
5 years. 
• For subjects in the CT Imaging Substudy, assessments using 4D CT 
at 30 days and 1 year will be done as listed below. Data will be 
evaluated by an independent CT core laboratory. 
- Assessment of leaflet mobility 
- Assessment of hypoattenuated leaflet thickening (HALT) 
- Assessment of leaflet thrombosis 
Note 2: At least 1 post-procedural echocardiogram must be obtained 
before discharge or 7 days (whichever comes first); if multiple 
echocardiographic studies are performed prior to discharge and within 7 
days of the procedure, the latest study performed will be used for 
analysis. 
Note 3: Echocardiography and NYHA assessment are not required in 
years 6, 8, and 9 (telephone follow-up only). 
Note 4: The mRS is required at all follow-up visits up to 5 years. For 
subjects diagnosed with a stroke, a neurological physical exam, mRS, 
and NIHSS must be performed after the event; mRS must also be 
administered at 90±14 days following a stroke; the simplified mRS 
questionnaire may be used for this follow-up assessment.   

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
a: Leon M, et al. J Am Coll Cardiol. 2011;57:253–69 
Kappetein AP, et al. J Am Coll Cardiol. 2012;60:1438–54 
Alu M, et al. An introduction to “VARC-3: a focused update.” 
Presented at SHDS, Chicago 2018.    
Method of 
Assigning 
Patients to 
Treatment 
Main Randomized Cohort: A computer generated list of random 
treatment allocations (randomization schedule) will be used to assign 
subjects to treatment in a 1:1 ratio of ACURATE to Control. A subset of 
subjects in the randomized cohort will also be enrolled in the 4D CT 
Imaging Substudy. 
Roll-In Cohort: For centers that do not have implantation experience 
with the ACURATE neo™ Aortic Bioprosthesis (transfemoral delivery) 
at least 2 Roll-In subjects will be treated before commencing treatment 
in the randomized cohort. Centers with prior experience with 
ACURATE are not required to do Roll-In cases. 
For the Main Randomized Cohort and the Roll-In Cohort, subjects will 
have a documented aortic annulus size of ≥21mm and ≤27mm based on 
pre-procedure diagnostic imaging. 
ACURATE Prime XL Nested Registry: Subjects will have a 
documented aortic annulus size of ≥26.5 mm and ≤29 mm based on pre-
procedure diagnostic imaging. 
ACURATE Extended Durability Study: A computer generated list of 
random treatment allocations (randomization schedule) will be used to 
assign subjects to treatment in a 1:1 ratio of ACURATE to Control. 
Only subjects considered to be at low surgical risk will be included in 
the Extended Durability Study. Randomization will be stratified by 
center and by intended control device. Subjects will receive ACURATE 
neo2 (S, M, or L valve sizes) or ACURATE Prime XL. Subjects with a 
documented aortic annulus size of ≥20.5mm and ≤27 mm may be 
enrolled in the Extended Durability Study after enrollment is concluded 
in the Main Randomized Cohort. Subjects with a documented aortic 
annulus size of ≥26.5mm and ≤29mm may be enrolled in the Extended 
Durability Study after enrollment is concluded in both the Main 
Randomized Cohort and the ACURATE Prime XL Nested Registry.  
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in the ACURATE Extended Durability 
Study. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
ACURATE Continued Access Study (CAS): Subjects will receive 
ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime XL. 
Subjects with a documented aortic annulus size of ≥20.5mm and ≤27mm 
may be enrolled in ACURATE CAS after enrollment is concluded in the 
Main Randomized Cohort. Subjects with a documented aortic annulus 
size of ≥26.5mm and ≤29mm may be enrolled in ACURATE CAS after 
enrollment is concluded in both the Main Randomized Cohort and the 
ACURATE Prime XL Nested Registry. Subjects at all surgical risk 
levels may be enrolled in ACURATE CAS but low-risk subjects will be 
considered for enrollment only after enrollment is completed in the 
Extended Durability Study. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE CAS.  
Follow-up 
Schedule 
All subjects implanted with a test or control device will be assessed at 
baseline, peri- and post-procedure, at discharge or 7 days post-procedure 
(whichever comes first), 30 days, 6 months, 1 year, and then annually 
for up to 10 years post-procedure. Subjects who are enrolled but not 
implanted with a test or control device at the time of the procedure will 
be followed for safety through 1 year. 
The visits at 30 days, 6 months, 1 ̶ 5 years, 7 years, and 10 years are to 
be an office/clinical/in-person or telehealth (https/telehealth.HHS.gov) 
visit (see Note 5 below) but may be done in-hospital should the subject 
be admitted at the time. Telephone follow-up is allowed at 6, 8, and 9 
years.  Procedures at each scheduled visit are described above under 
“Additional Measurements.”  
Note 5: For subjects in the CT Imaging Substudy, the visits at 30 days 
and 1 year must be done in the clinic (or in-hospital). 
Study Duration Subjects implanted with a test or control device will be followed for 
10 years after the index procedure.  
Enrollment is expected to be completed in approximately 62 months; 
therefore, the total study duration is estimated to be approximately 
16 years. 
Participant 
Duration 
The study duration for each subject is expected to be approximately 
10 years. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
Adjunctive 
Pharmacologic 
Therapy 
Anticoagulant Therapy 
Anticoagulant therapy (e.g., unfractionated heparin) per local standard 
of care must be administered during the implant procedure, with a 
recommended target activated clotting time of ≥250 seconds during the 
index procedure. 
Anti-Platelet Therapy 
Per US society guidelinesb, antiplatelet therapy is recommended after 
TAVR to decrease the risk of thrombotic or thromboembolic 
complications if there are no contraindications to these medications. 
ACURATE IDE study subjects must receive antiplatelet therapy (aspirin 
and/or a P2Y12 inhibitor) for at least 1 month following valve implant 
(see below for recommended doses). It should be noted, however, that 
recent clinical evidence points to increased bleeding risk post TAVR 
among subjects receiving dual antiplatelet therapy or antiplatelet therapy 
plus anti-coagulation (among subjects indicated for anti-coagulation)c. 
Aspirin 
A loading dose of aspirin (recommended dose of 75–325 mg) is 
recommended for subjects who have not been on aspirin therapy for 
≥72 hours at the time of the index procedure. The loading dose should 
be administered prior to the implant procedure. Subjects who have been 
taking aspirin daily for ≥72 hours at the time of the index procedure do 
not require a loading dose. 
After the valve implant procedure, the recommended aspirin dose is 
≥75 mg daily. It is recommended that daily aspirin be given indefinitely 
as per local standard of care.  
P2Y12 Inhibitor 
A loading dose of a P2Y12 inhibitor (recommended dose of ≥300 mg for 
clopidogrel, 60 mg for prasugrel, 180 mg for ticagrelor) is recommended 
for subjects who have not been on P2Y12 therapy for ≥72 hours at the 
time of the index procedure. The loading dose should be administered 
prior to the implant procedure. 
After the valve implant procedure, a P2Y12 inhibitor and/or aspirin is 
required for at least 1 month. 
Note 6: Anti-platelet therapy dosing and the type of P2Y12 inhibitor 
used should be according to the local standard of care.  
Note 7: If a subject requires chronic anticoagulation, either a P2Y12 
inhibitor or aspirin is recommended prior to and after the implant 
procedure in addition to the anticoagulant therapy (but both aspirin and 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
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a P2Y12 inhibitor are not recommended). After the implant procedure, 
the subject should be treated with an oral anticoagulant and either a 
P2Y12 inhibitor or aspirin for at least 1 month.  
Note 8: Subjects who are expected to undergo chronic anticoagulation 
therapy after the TAVR procedure are not eligible to be included in the 
4D CT Imaging Substudy (see Additional Exclusion Criteria below). 
b:  Otto CM, et al. J Am Coll Cardiol. 2021;77:e25-e197 
c: Nijenhuis VJ, et al. N Engl J Med 2020;382:1696–1707 
Brouwer J, et al. N Engl J Med 2020;383:1447–1457 
Inclusion 
Criteria 
IC1. 
Subject has documented severe symptomatic native aortic 
stenosis defined as follows: aortic valve area (AVA) ≤1.0 cm2 (or 
AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 
mmHg, OR maximal aortic valve velocity ≥4.0 m/s, OR Doppler 
velocity index ≤0.25 as measured by echocardiography and/or 
invasive hemodynamics.  
Note 9: In cases of low flow, low gradient aortic stenosis with 
left ventricular dysfunction (ejection fraction <50%), dobutamine 
can be used to assess the grade of aortic stenosis (maximum 
dobutamine dose of 20 mcg/kg/min recommended)b; the subject 
may be enrolled if echocardiographic criteria are met with this 
augmentation. 
IC2. 
Subject has a documented aortic annulus size of ≥20.5 mm and 
≤29 mm based on the center’s assessment of pre-procedure 
diagnostic imaging (and confirmed by the Case Review 
Committee [CRC]) and, for the Main Randomized Cohort and 
Extended Durability Study, is deemed treatable with an available 
size of both test and control device. 
IC3. 
For subjects with symptomatic aortic valve stenosis per IC1 
definition above, functional status is NYHA Functional 
Class ≥ II. 
IC4. 
Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees that 
the subject is indicated for TAVR, is likely to benefit from valve 
replacement, and TAVR is appropriate.  
IC5. 
Subject (or legal representative) understands the study 
requirements and the treatment procedures and provides written 
informed consent. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
IC6. 
Subject, family member, and/or legal representative agree(s) and 
subject is capable of returning to the study hospital for all 
required scheduled follow up visits. 
IC7. 
Subject is expected to be able to take the protocol-required 
adjunctive pharmacologic therapy. 
b: Otto CM, et al. J Am Coll Cardiol. 2021;77:e25-e197 
Exclusion 
Criteria 
Vulnerable subjects (ISO 14155) will not be enrolled in ACURATE 
IDE. 
EC1. Subject has a unicuspid or bicuspid aortic valve. 
EC2. Subject has had an acute myocardial infarction within 30 days 
prior to the index procedure (defined as Q-wave MI or non–Q-
wave MI with total CK elevation ≥ twice normal in the presence 
of CK-MB elevation and/or troponin elevation). 
EC3. Subject has had a cerebrovascular accident or transient ischemic 
attack clinically confirmed by a neurologist or neuroimaging 
within the past 6 months prior to study enrollment. 
EC4. Subject is on renal replacement therapy or has eGFR <20. 
EC5. Subject has a pre-existing prosthetic aortic or mitral valve. 
EC6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation. 
EC7. Subject has moderate or severe mitral stenosis (mitral valve area 
≤1.5 cm2 and diastolic pressure half-time ≥150 ms, Stage C or 
Db). 
EC8. Subject has a need for emergency surgery for any reason. 
EC9. Subject has a history of endocarditis within 6 months of index 
procedure or evidence of an active systemic infection or sepsis. 
EC10. Subject has echocardiographic evidence of new intra-cardiac 
vegetation or intraventricular or paravalvular thrombus requiring 
intervention. 
EC11. Subject has platelet count <50,000 cells/mm3 or >700,000 
cells/mm3, or white blood cell count <1,000 cells/mm3. 
EC12. Subject has had a gastrointestinal bleed requiring hospitalization 
or transfusion within the past 3 months or has other clinically 
significant bleeding diathesis or coagulopathy that would 

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preclude treatment with required antiplatelet regimen or will 
refuse transfusions. 
EC13. Subject has known hypersensitivity to contrast agents that cannot 
be adequately pre-medicated or has known hypersensitivity to the 
protocol required medications (aspirin, all P2Y12 inhibitors, 
heparin), or to the individual components of the test or control 
valve (nickel, titanium, stainless steel, platinum, iridium or 
polyethylene terephthalate [PET]). 
EC14. Subject has a life expectancy of less than 12 months due to non-
cardiac, comorbid conditions based on the assessment of the 
investigator at the time of enrollment. 
EC15. Subject has hypertrophic cardiomyopathy. 
EC16. Subject has any therapeutic invasive cardiac or vascular 
procedure within 30 days prior to the index procedure (except for 
balloon aortic valvuloplasty, pacemaker implantation, or 
implantable cardioverter defibrillator implantation, which are 
allowed). 
EC17. Subject has untreated coronary artery disease, which in the 
opinion of the treating physician is clinically significant and 
requires revascularization. 
EC18. Subject has severe left ventricular dysfunction with ejection 
fraction <20%. 
EC19. Subject is in cardiogenic shock or has hemodynamic instability 
requiring inotropic support or mechanical support devices. 
EC20. Subject has arterial access that is not acceptable for the study 
device (test or control) delivery systems as defined in the device 
(test or control) Directions For Use. 
EC21. Subject has either of the following: 
• Severe vascular disease that would preclude safe access (e.g., 
aneurysm with thrombus that cannot be crossed safely; 
marked tortuosity; significant narrowing of the abdominal 
aorta; severe unfolding of the thoracic aorta; or thick, 
protruding, ulcerated atheroma in the aortic arch), OR 
• Severe/eccentric calcification of the aortic annulus that would 
prevent safe implantation of the TAVR prosthesis. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
EC22. Subject has current problems with substance abuse (e.g., alcohol, 
etc.) that may interfere with the subject’s participation in this 
study. 
EC23. Subject is participating in another investigational drug or device 
study that has not reached its primary endpoint or subject intends 
to participate in another investigational device clinical trial 
within 12 months after index procedure. 
EC24. Subject has untreated conduction system disorder (e.g., Type II 
second degree atrioventricular block) that in the opinion of the 
treating physician is clinically significant and requires a 
pacemaker implantation. Enrollment is permissible after 
permanent pacemaker implantation. 
EC25. Subject has severe incapacitating dementia. 
b: Otto CM, et al. J Am Coll Cardiol. 2021;77:e25-e197 
Additional 
Exclusion 
Criteria 
Additional exclusion criteria apply to subjects considered for enrollment 
in the CT Imaging Substudy as listed below. 
AEC1. Subject has eGFR <30 mL/min (chronic kidney disease 
stage IV or stage V). 
AEC2. Subject has atrial fibrillation that cannot be rate controlled to 
ventricular response rate < 60 bpm. 
AEC3. Subject is expected to undergo chronic anticoagulation therapy 
after the index procedure. 
 
Note 10: Subjects treated with short-term anticoagulation post 
procedure can be included in the CT Imaging Substudy; in 
these subjects the 30-day imaging will be performed 30 days 
after discontinuation of anticoagulation. 
Statistical Methods 
Analysis Sets 
Analysis sets for the ACURATE IDE Main Randomized Cohort and the 
Extended Durability Study are listed below. Subjects in the Main 
Randomized Cohort and the Extended Durability Study are considered 
enrolled in the study upon randomization. 
 - Intention-To-Treat (ITT): This population includes all subjects who 
sign an Informed Consent Form, are enrolled in the trial, and are 
randomized, whether or not an assigned study device is implanted. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
 - Implanted: This population includes all subjects who sign an 
Informed Consent Form, are enrolled in the trial, and are implanted 
with the assigned (control versus test), randomized study device. 
Note 11: For the Main Randomized Cohort and Extended Durability 
Study, if a subject receives 2 different valve types from 2 different 
manufacturers, the subject will be excluded from the Implanted analysis. 
Among the Roll-In, ACURATE Prime XL, and Continued Access Study 
cohorts, for the ITT analysis, all subjects who sign an Informed Consent 
Form and are enrolled in the study will be included in the analysis 
sample, regardless of whether the test device was implanted. The 
Implanted analysis set will include all subjects who sign an Informed 
Consent Form and are implanted with an ACURATE valve. For these 
single-arm cohorts, the subject is considered enrolled in the trial when 
there is an attempt made to insert the ACURATE Transfemoral Aortic 
Valve System into the subject’s femoral artery. 
Primary 
Endpoint 
Statistical 
Hypothesis 
In the Main Randomized Cohort, the primary endpoint (composite of 
all-cause mortality, all stroke, and rehospitalization at 1 year) rate for the 
ACURATE group is non-inferior to that for the Control group. 
Statistical Test 
Method for the 
Primary 
Endpoint 
For the Main Randomized Cohort, the statistical hypothesis is that the 
primary endpoint rate for ACURATE is non-inferior to the rate for 
Control: 
 
H0: PE_ACURATE minus PE_Control ≥ Δ (Inferior) 
 
H1: PE_ACURATE minus PE_Control < Δ (Non-inferior) 
where PE_ACURATE and PE_Control correspond to the primary endpoint 
rates for the ACURATE group (test) and the Control group, 
respectively, and Δ is the non-inferiority margin. 
The primary analysis set for the primary endpoint is the ITT analysis set. 
This endpoint will also be analyzed for the implanted analysis set. 
A Bayesian analysisd will be performed to estimate the treatment 
difference between ACURATE and Control through posterior 
probability. Details are shown below.  
d: Popma JJ, et al. N Engl J Med 2019;380:1706-15 
Reardon MJ, et al. N Engl J Med 2017;376:1321-31 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
Implantation of ACURATE in Subjects InDicatEd for TAVR 
Sample Size 
Parameters for 
the Primary 
Endpoint 
Although the primary endpoint analysis is performed using the Bayesian 
method, the sample size calculation for the randomized cohort (see Note 
12 below) is based on a standard non-inferiority two-sample test 
approach. The sample size calculation for the primary endpoint is based 
on the following assumptions. 
• Expected rate for both arms = 22.3% (based on weighted average of 
TAVR datae; see Note 13 below) 
• Non-inferiority margin (Δ) = 8.0% (36% relative to the expected 
rate) 
• Test significance level (α) = 0.025 (1-sided) (see Note 14 below) 
• Test (ACURATE): Control ratio = 1:1 
• Power (1 minus ß) > 90%  
• Expected rate of attrition = 5% 
• Total sample size = 1500 (750 per group) 
• Number of evaluable subjects per group = 712 
• Analyses: One administrative, one formal interim, one final (see 
Note 15 below) 
Note 12: The Pocock-type methodf is used during sample size 
calculations. The statistical software EAST® 6.5 is used for the sample 
size calculations. 
Note 13: The estimated proportions of subjects by operative risk level is 
10% extreme risk, 25% high risk, 30% intermediate risk, and 35% low 
risk.  
Note 14: A statistically equivalent posterior probability threshold for the 
Bayesian analysis is empirically chosen through extensive simulations 
and is pre-specified in the Statistical Analysis Plan (SAP). 
Note 15: The administrative interim analysis will be conducted when 
the first 350 subjects in the Main Randomized Cohort have completed 1-
year follow-up. The formal interim analysis will be carried out after 
enrollment in the Main Randomized Cohort is completed. This formal 
interim analysis will be conducted on the full N=1500 subject cohort of 
the Main Randomized Cohort after the first 1050 subjects in the Main 
Randomized Cohort have completed 1-year follow-up. The piecewise 
exponential modelg based on outcomes among these subjects will be 
used to predict the 1-year results by treatment group for the remaining 
enrolled subjects. The Bayesian method will be used to perform the 
hypothesis testing on the combined data sets. A final analysis for the 

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primary endpoint will be performed on all subjects with completed 1-
year data if non-inferiority cannot be claimed at the formal interim 
analysis (see Success Criteria below). 
e: Adams DH, et al. N Engl J Med 2014;370:1790-8 
Mack MJ, et al. N Engl J Med 2019;380:1695-705 
Popma JJ, et al. J Am Coll Cardiol 2014;63:1972-81 
Popma JJ, et al. N Engl J Med 2019;380:1706-15 
Reardon MJ, et al. N Engl J Med 2017;376:1321-31 
Smith CR, et al. N Engl J Med 2011;364:2187-98 
Thourani VH, et al. Lancet 2016;387:2218-25 
Waksman R, et al. J Am Coll Cardiol Intv 2019;12:901–7 
Webb JG, et al. J Am Coll Cardiol Intv 2015;8:1797-806 
Medtronic CoreValve System PMA P130021/S002: FDA Summary of 
Safety and Effectiveness Data 
f: Lan KKG and DeMets DL. Biometrika 1983;70:659–63 
g: Popma JJ, et al. N Engl J Med 2019;380:1706-15 
Success Criteria 
for the Primary 
Endpoint 
The Bayesian method is used to test the non-inferiority hypothesis of the 
primary endpoint on the Main Randomized Cohort. To establish that the 
ACURATE device is non-inferior to the Control, the results will need to 
meet the following equation: 
Pr(H1 | Data) > ξ   
where  
• Pr(H1 | Data) is the posterior probability of H1 given the observed 
data at either the interim or the final analysis;  
• H1 is the alternative hypothesis for non-inferiority: 
PE_ACURATE  minus PE_Control < Δ; 
• ξ is a prespecified threshold, which is empirically chosen through 
extensive simulations using the Bayesian approach for the non-
inferiority tests.  
If non-inferiority has been declared at the formal interim analysis, 
the non-inferiority test will not be performed at the final analysis. If non-
inferiority cannot be declared at this interim analysis, the non-inferiority 
test will be performed at the final analysis for all subjects using the 
Bayesian method with the same pre-specified threshold. The study will 
not stop for futility at the interim analysis. 
The detailed study operating characteristics and simulation results will 
be provided in the SAP. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
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ACURATE 
Prime XL 
Nested Registry 
Statistical 
Hypothesis 
Mean aortic valve pressure gradient at 30 days post implant procedure is 
less than a performance goal (PG): 
H0: Gradient30D ≥ PG 
H1: Gradient30D < PG  
where Gradient30D is the 30-day mean aortic valve pressure gradient for 
the ACURATE Prime XL valve and PG is 15 mmHg. 
Statistical Test 
Method for the 
ACURATE 
Prime XL 
Nested Registry 
A one-sample t-test will be used to test the one-sided hypothesis at a 
significance level of 2.5%. 
Sample Size 
Parameters for 
the ACURATE 
Prime XL 
Nested Registry 
• Expected 30-day mean pressure gradient from ACURATE Prime XL 
= 10 mmHgh 
• Expected standard deviation = 7 mmHg  
• PG = 15 mmHg 
• Test significance level (α) = 0.025 (1-sided) 
• Power > 90% 
• Evaluable number of subjects = Minimum of 40 subjects 
• Expected rate of attrition = 20% (8 subjects) 
• Planned enrollment of 50 subjects  
• The analysis population for the hypothesis testing will be the subject 
population implanted with the ACURATE Prime XL valve.    
h: Based on Boston Scientific data on file and published data for large-
annulus CoreValve devices: 
Tang GHL, et al. Am J Cardiol 2019;124:1091-8 
Kalogeras K, et al. Catheter Cardiovasc Interv 2019;93:685-91 
Ussia GP, et al. EuroIntervention 2015;10:e1-e8 
Success Criteria 
for the 
ACURATE 
Prime XL 
Nested Registry 
If the P value from the one-sample t-test is < 0.025, the ACURATE 
Prime XL valve will be concluded to have a 30-day mean aortic valve 
pressure gradient < 15 mmHg. This corresponds to the one-sided upper 
2.5% confidence bound of the observed 30-day mean aortic valve 
pressure gradient being < 15 mmHg. 

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ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve through 
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Statistics 
Summary 
Data will be summarized separately for each cohort. In addition to the 
hypothesis tests listed above, descriptive statistics will be used. Full 
methods will be described in the Statistical Analysis Plan. 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................3 
3. 
TABLE OF CONTENTS .......................................................................................................23 
3.1. Table of Figures .....................................................................................................28 
3.2. Table of Tables ......................................................................................................29 
4. 
INTRODUCTION ................................................................................................................30 
4.1. Background ............................................................................................................30 
4.1.1. 
Aortic Stenosis ..........................................................................................30 
4.1.2. 
Transcatheter Aortic Valve Implantation/Replacement ...........................30 
4.2. Study Rationale .....................................................................................................34 
5. 
DEVICE DESCRIPTION ......................................................................................................35 
5.1. ACURATE Transfemoral Aortic Valve System (Test)......................................35 
5.1.1. 
ACURATE neo2™ Aortic Valve and ACURATE Prime™ Aortic Valve 
XL .............................................................................................................35 
5.1.2. 
ACURATE neo2 Transfemoral Delivery System and ACURATE Prime 
Transfemoral Delivery System XL ...........................................................38 
5.1.3. 
Introducer Set ............................................................................................40 
5.2. Control Device .......................................................................................................40 
5.3. Device Labeling .....................................................................................................40 
5.3.1. 
Test Device ...............................................................................................40 
5.3.2. 
Control Device ..........................................................................................41 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................41 
6.1. Study Objectives ....................................................................................................41 
6.2. Study Endpoints ....................................................................................................41 
6.3. Primary Endpoint .................................................................................................42 
6.4. Additional Measurements ....................................................................................42 
6.5. Overview of Objectives and Endpoints ...............................................................44 
7. 
STUDY DESIGN .................................................................................................................45 
7.1. Scale and Duration ................................................................................................45 

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7.2. Treatment Assignment..........................................................................................48 
7.2.1. 
Treatment and Control ..............................................................................49 
7.3. Justification for the Study Design ........................................................................50 
8. 
SUBJECT SELECTION ........................................................................................................51 
8.1. Study Population and Eligibility ..........................................................................51 
8.2. Inclusion Criteria ..................................................................................................51 
8.3. Exclusion Criteria .................................................................................................52 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................54 
9.1. Point of Enrollment ...............................................................................................54 
9.1.1. 
Roll-In Subjects ........................................................................................54 
9.1.2. 
Main Randomized Cohort Subjects ..........................................................54 
9.1.3. 
ACURATE Prime™ XL Nested Registry Subjects .................................54 
9.1.4. 
ACURATE Extended Durability Study Subjects .....................................54 
9.1.5. 
ACURATE Continued Access Study Subjects .........................................54 
9.2. Discontinuation of Study Intervention ................................................................54 
9.3. Withdrawal ............................................................................................................55 
9.4. Lost to Follow-Up ..................................................................................................55 
9.5. End-of-Study Definition .......................................................................................56 
10. STUDY METHODS .............................................................................................................56 
10.1. Data Collection ......................................................................................................56 
10.2. Study Candidate Screening ..................................................................................63 
10.2.1. Strategies for Recruitment and Retention .................................................63 
10.3. Subject Informed Consent ....................................................................................64 
10.4. Screening Assessments ..........................................................................................64 
10.5. Baseline Assessments ............................................................................................66 
10.6. Pre-procedure Medications ..................................................................................67 
10.7. Index Procedure ....................................................................................................68 
10.7.1. Control Cohort ..........................................................................................68 
10.7.2. ACURATE Transfemoral Aortic Valve System (Test) Cohort ................69 
10.7.2.1. Valvuloplasty ...........................................................................69 
10.7.2.2. Preparing and Using the ACURATE Transfemoral Aortic 
Valve System ...........................................................................69 

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10.8. Post Index Procedure ............................................................................................72 
10.9. Prior to Discharge or 7 Days Post-Procedure (Whichever Comes First) ........73 
10.10. 
Follow-up .................................................................................................74 
10.10.1. 30-Day Follow-up (30±7 Days) ................................................................74 
10.10.2. 6-Month Follow-up (180±30 Days) ..........................................................75 
10.10.3. 1-Year Follow-up (365±30 Days) ............................................................76 
10.10.4. Annual Follow-up (±45 Days) to 5 Years ................................................77 
10.10.5. Follow-up (±60 Days) at 7 and 10 Years ..................................................78 
10.10.6. Follow-up (±60 Days) at 6, 8 and 9 Years ................................................78 
10.11. 
Study Completion ...................................................................................79 
10.12. 
Source Documents ..................................................................................79 
10.13. 
Local Laboratory/Vendor Documentation ...........................................79 
11. STATISTICAL CONSIDERATIONS ......................................................................................80 
11.1. Endpoints ...............................................................................................................80 
11.1.1. Primary Endpoint ......................................................................................80 
11.1.1.1. Statistical Hypothesis for the Primary Endpoint – Main 
Randomized Cohort .................................................................80 
11.1.1.2. Sample Size Parameters for the Primary Endpoint – Main 
Randomized Cohort .................................................................81 
11.1.1.3. Success Criteria for the Primary Endpoint – Main Randomized 
Cohort ......................................................................................82 
11.1.1.4. Statistical Methods – Primary Endpoint – Main Randomized 
Cohort ......................................................................................82 
11.1.2. ACURATE Prime XL Nested Registry Statistical Assessment ...............83 
11.1.2.1. Statistical Hypothesis – ACURATE Prime XL Nested Registry
..................................................................................................83 
11.1.2.2. Sample Size Parameters for the ACURATE Prime XL Nested 
Registry ....................................................................................83 
11.1.2.3. Success Criteria for the ACURATE Prime XL Nested Registry
..................................................................................................83 
11.1.3. Baseline Comparability ............................................................................84 
11.1.4. Post-procedure Measurements ..................................................................84 
11.2. General Statistical Methods .................................................................................84 
11.2.1. Analysis Sets .............................................................................................84 
11.2.2. Control of Systematic Error/Bias ..............................................................85 
11.2.3. Number of Subjects Per Investigative Center ...........................................85 
11.2.4. Randomization Scheme ............................................................................85 

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11.2.5. Reporting Events ......................................................................................86 
11.3. Data Analyses ........................................................................................................86 
11.3.1. Other Measurements .................................................................................86 
11.3.2. Interim/Administrative Analyses ..............................................................86 
11.3.3. Subgroup Analyses for Main Randomized Cohort Subjects ....................87 
11.3.4. Justification of Pooling .............................................................................87 
11.3.5. Multivariable Analyses .............................................................................87 
11.3.6. Changes to Planned Analyses ...................................................................87 
12. HEALTH ECONOMICS OUTCOMES ...................................................................................88 
13. DATA MANAGEMENT .......................................................................................................88 
13.1. Data Collection, Processing, and Review ............................................................88 
13.2. Data Retention .......................................................................................................88 
13.3. Core Laboratories .................................................................................................89 
13.3.1. Echocardiography Core Laboratory .........................................................89 
13.3.2. CT and Angiography Core Laboratory .....................................................89 
13.3.3. Histopathology Core Laboratory ..............................................................89 
14. DEVIATIONS .....................................................................................................................89 
15. DEVICE ACCOUNTABILITY ..............................................................................................90 
15.1. Device Accountability for Products Labelled Investigational ...........................90 
15.2. Device Accountability for the Control Device ....................................................91 
16. COMPLIANCE ....................................................................................................................91 
16.1. Statement of Compliance ......................................................................................91 
16.2. Investigator Responsibilities ................................................................................91 
16.2.1. Delegation of Responsibility ....................................................................93 
16.3. Institutional Review Board/Research Ethics Board/Human Research Ethics 
Committee/ Independent Ethics Committee .......................................................94 
16.4. Sponsor Responsibilities .......................................................................................94 
16.4.1. Role of Boston Scientific Corporation Representatives ...........................94 
16.4.2. Training with the Investigational Device .................................................95 
16.5. Insurance ................................................................................................................96 
17. MONITORING ....................................................................................................................96 

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18. POTENTIAL RISKS AND BENEFITS ...................................................................................97 
18.1. Anticipated Adverse Events and Risks Associated with Transcatheter Aortic 
Valve Replacement ................................................................................................97 
18.1.1. Reduced Leaflet Motion/Leaflet Thrombosis ...........................................99 
18.2. Risks Associated with the Study Device(s) ..........................................................99 
18.3. Risks Associated with Participation in the Clinical Study ................................99 
18.4. Possible Interactions with Concomitant Medical Treatments ..........................99 
18.5. Risk Minimization Actions .................................................................................100 
18.6. Anticipated Benefits ............................................................................................101 
18.6.1. Potential Benefits to the TAVR Procedure .............................................101 
18.6.2. Potential Benefit Using the ACURATE Transfemoral Aortic Valve 
System.....................................................................................................101 
18.7. Risk to Benefit Rationale ....................................................................................102 
19. SAFETY REPORTING .......................................................................................................102 
19.1. Reportable Events by Investigational Center to Boston Scientific .................102 
19.2. Definitions and Classification ............................................................................104 
19.3. Relationship to Study Device(s) .........................................................................106 
19.4. Investigator Reporting Requirements ...............................................................107 
19.5. Device Deficiencies ..............................................................................................109 
19.5.1. Boston Scientific Device Deficiencies ...................................................109 
19.5.2. Control Device Deficiencies ...................................................................110 
19.6. Reporting to Regulatory Authorities / IRBs / REBs / HRECs / IECs / 
Investigators ........................................................................................................110 
20. INFORMED CONSENT......................................................................................................110 
21. COMMITTEES .................................................................................................................112 
21.1. Safety Monitoring Process ..................................................................................112 
21.1.1. Clinical Events Committee .....................................................................112 
21.1.2. Data Monitoring Committee ...................................................................112 
21.2. Case Review Committee .....................................................................................112 
21.3. Steering Committee .............................................................................................113 
22. SUSPENSION OR TERMINATION .....................................................................................113 
22.1. Premature Termination of the Study ................................................................113 

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22.1.1. Criteria for Premature Termination of the Study ....................................113 
22.2. Termination of Study Participation by the Investigator or Withdrawal of IRB 
/ REB / HREC / IEC Approval ..........................................................................113 
22.3. Requirements for Documentation and Subject Follow-up ..............................114 
22.4. Criteria for Suspending/Terminating a Study Center .....................................114 
23. STUDY REGISTRATION AND RESULTS ...........................................................................114 
23.1. Study Registration ...............................................................................................114 
23.2. Clinical Investigation Report .............................................................................114 
23.3. Publication Policy ................................................................................................115 
24. BIBLIOGRAPHY ...............................................................................................................115 
25. ABBREVIATIONS AND DEFINITIONS ...............................................................................123 
25.1. Abbreviations ......................................................................................................123 
25.2. Definitions ............................................................................................................125 
26. REVISION HISTORY ........................................................................................................140 
26.1. Summary of Protocol Revision History ............................................................140 
 
3.1. 
Table of Figures 
Figure 5.1-1: ACURATE Aortic Valve .................................................................................. 37 
Figure 5.1-2: ACURATE neo2 Transfemoral Delivery System – Overview ......................... 38 
Figure 5.1-3: ACURATE neo2 Transfemoral Delivery System – Distal End ........................ 38 
Figure 5.1-4: Insertion Aid Positioned over the Delivery System .......................................... 39 
Figure 5.1-5: ACURATE Prime™ Transfemoral Delivery System XL – Overview ............. 39 
Figure 5.1-6: ACURATE Prime™ Transfemoral Delivery System XL – Distal End with 
Loaded ACURATE Prime™ Aortic Valve XL ................................................... 39 
Figure 7.1-1: ACURATE IDE Study Design ......................................................................... 48 
Figure 10.1-1: Data Collection Schedule for ACURATE IDE............................................... 62 
Figure 10.7-1: Valve Implantation Procedure ........................................................................ 71 
 

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3.2. 
Table of Tables 
Table 4.1-1: TAVR Outcomes at 30 Days and 1 Year – Transfemoral Access ..................... 31 
Table 5.1-1: ACURATE neo2 and ACURATE Prime Aortic Valve Size Chart – Main 
Randomized Cohort, Roll-In Cohort and ACURATE Prime XL Nested Registry
 ............................................................................................................................. 36 
Table 5.1-2: ACURATE neo2 and ACURATE Prime Aortic Valve Size Chart – Extended 
Durability Study and Continued Access Study ................................................... 36 
Table 6.4-1: Neurological Events in ACURATE IDE ............................................................ 44 
Table 6.5-1: Overview of Objectives and Endpoints .............................................................. 45 
Table 7.1-1: Devices and Risk Levels for ACURATE IDE Cohorts ..................................... 47 
Table 7.2-1: Treatment and Control Devices .......................................................................... 49 
Table 8.2-1: ACURATE IDE Inclusion Criteria .................................................................... 51 
Table 8.3-1: ACURATE IDE Exclusion Criteria ................................................................... 52 
Table 8.3-2: ACURATE IDE Additional Exclusion Criteria for the 4D CT Imaging Substudy
 ............................................................................................................................. 53 
Table 10.1-1: Data Collection Schedule for ACURATE IDE ................................................ 58 
Table 10.12-1: Source Documentation Requirements ............................................................ 79 
Table 18.1-1: Risks Associated with Transcatheter Aortic Valve Replacement .................... 98 
Table 19.2-1: Safety Definitions ........................................................................................... 104 
Table 19.3-1: Criteria for Assessing Relationship of Study Device and Procedure to Adverse 
Event .................................................................................................................. 106 
Table 19.4-1: Investigator Reporting Requirements ............................................................. 108 
Table 25.1-1: Abbreviations and Acronyms ......................................................................... 123 
Table 25.2-1: Definitions ...................................................................................................... 125 
Table 26.1-1: Revision History ............................................................................................. 141 
 
 

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4. Introduction 
This protocol specifies procedures and contains information relevant to the clinical 
evaluation of the ACURATE™ Transfemoral Aortic Valve System, which is a transcatheter 
aortic valve implantation/replacement (TAVI/TAVR) device designed and manufactured by 
Boston Scientific Corporation, Marlborough, MA, USA. 
4.1. 
Background 
4.1.1. 
Aortic Stenosis 
The incidence of aortic stenosis (AS), which most commonly occurs in the very elderly, is 
increasing due to the aging of the world-wide population and the lack of drug therapies to 
prevent, halt, or effectively slow the stenotic process1-3. It is estimated that nearly 5% of 
elderly ≥75 years of age have AS and its prevalence is expected to increase due to an aging 
population2,3. Aortic stenosis is associated with high rates of death and complications after 
the appearance of symptoms2,3.  
Many patients with severe and symptomatic aortic stenosis are successfully treated with 
surgical aortic valve replacement (SAVR), which can reduce symptoms and improve 
survival2-5. However, up to one-third of patients with severe AS are not treated with SAVR 
because of their comorbidities and consequent perioperative risk6-8. With standard medical 
therapy, mortality after 1 year among these patients may be as high as 50%2,3,8. Percutaneous 
transluminal aortic valvuloplasty, which was introduced as an alternative to SAVR in elderly 
and/or high-risk surgical patients, can provide symptomatic relief and/or temporary 
improvement but does not provide definitive treatment in patients with severe calcific AS3,5. 
It is also associated with relatively high mortality and complication rates3,9. As described 
below in Section 4.1.2, transcatheter aortic valve implantation/replacement provides another 
alternative to SAVR in select patients4,5,10. 
4.1.2. 
Transcatheter Aortic Valve Implantation/Replacement 
There are several approaches to TAVR, including transfemoral (TF), transapical (TA), 
transaortic (TAo), transaxillary/subclavian, transcarotid, and transcaval2,11. Patients generally 
undergo a joint interdisciplinary screening process, including comprehensive multimodality 
imaging12-15, prior to procedure recommendation. Because of the limitations of existing 
surgical risk scores, center heart teams also consider other co-morbidities and patient frailty 
to fully characterize risk16.  
The use of TAVR has produced significant reductions in mortality and repeat hospitalization 
compared to medical therapy8,17,18. In selected patients considered to be at high surgical risk, 
TAVR has resulted in similar19-21 or lower22-24 mortality when compared to SAVR. 
Continuous procedural refinements and device improvements have aimed to widen 
application to lower risk patients25,26 and randomized controlled trials (RCT) have shown 
similar outcomes among intermediate-risk and low-risk surgical patients treated with TAVR 
or SAVR27-30. Meta-analyses have also shown similar long-term survival after TAVR 

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compared to SAVR31,32. Currently, TAVR is approved for use in AS patients considered 
inoperable or at low to high surgical risk and expert consensus documents have outlined 
TAVR patient selection criteria4,5,11,33.   
Table 4.1-1 summarizes outcomes at 30 days and 1 year from some TAVR studies that 
enrolled subjects similar to those planned for this study. 
Table 4.1-1: TAVR Outcomes at 30 Days and 1 Year – Transfemoral Access 
Study  
Device/N 
All-
cause 
Death  
Disabling
/ Major 
Stroke 
Major 
VC 
LT 
Bleeding  
AKI 
PPM 
30-Day Outcomes – Randomized Studies 
PARTNER 1Aa 
(2011)19 
SAPIEN / 244† 
3.3 
2.9 
14.0 
9.5b 
2.5c 
3.7 
PARTNER 2Ad 
(2016)27 
SAPIEN XT / 775* 
3.0 
2.3 
8.5 
6.7 
0.5e 
8.1 
PARTNER 2Bf 
(2015)34 
SAPIEN XT / 284† 
SAPIEN / 276† 
3.5 
5.1 
3.2 
3.0 
9.5 
15.2 
7.8 
12.4 
15.4g 
16.8g 
6.8 
5.9 
PARTNER 3f 
(2019)29 
SAPIEN 3 / 496# 
0.4 
0.0 
2.2 
1.2 
0.4h   
6.5 
CoreValve High 
Riski (2014)22 
CoreValve / 390† 
3.3 
3.9 
5.9 
13.6 
6.0g 
19.8 
NOTIONj 
(2015)35 
CoreValve / 142‡ 
2.1 
1.4k 
5.6 
11.3l 
0.7h 
34.1 
SURTAVIm 
(2017)28 
CoreValve / 864* 
2.2 
1.2 
6.0 
12.2 
1.7h 
25.9 
CoreValve Low 
Riski(2019)30 
CoreValve, 
Evolut R, Evolut 
PRO / 725# 
0.5 
0.5 
3.8 
2.4 
0.9h 
17.4 
CHOICEf 
(2014)36 
SAPIEN XT / 121† 
CoreValve / 117† 
4.1 
5.1 
2.5 
2.6 
9.9 
11.1 
8.3b 
12.0b 
4.1e 
9.4e 
17.3 
37.6 
REPRISE IIIf 
(2018)37 
Lotus Valven / 607† 
CoreValven / 305† 
2.5 
2.3 
2.0 
3.3 
7.0 
5.3 
8.0 
5.0 
2.5h 
3.6h 
29.1 
15.8 
PORTICO IDEo 
(2020)38 
Portico / 381† 
Commercial / 369† 
3.5 
1.9 
1.6 
1.1 
9.6 
6.3 
5.9 
3.8 
1.9e 
1.1e 
27.7 
11.6 
30-Day Outcomes – Single-Arm Studies 
PARTNER 
NRCAf (2014)39 
SAPIEN / 1023† 
4.3 
2.4 
8.0 
6.8b 
1.6e 
– 
SAPIEN 3p 
(2016)40 
SAPIEN 3 / 953* 
SAPIEN 3 / 491† 
1.1 
1.6 
0.7 
0.8 
6.3 
5.5 
3.6 
5.5 
0.8h 
1.2h 
10.5 
13.5 
CoreValve 
Extreme Riskq 
(2014)41 
CoreValve / 489† 
8.4 
2.3 
8.2 
12.7 
11.8 
21.6 
Evolut R First 
in Manr (2015)42 
Evolut R / 60† 
0.0 
0.0k 
8.3 
5.0 
1.7h 
9.8 
CoreValve – 
Large Annulis 
(2015)43 
CoreValve 31mm / 
76† 
2.6 
0.0k 
6.6 
2.6t 
1.3h 
23.7 
EVOLUT R US 
Studyu(2017)44 
Evolut R / 241† 
2.5 
3.3 
7.5 
7.1 
1.2h 
16.4 

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Table 4.1-1: TAVR Outcomes at 30 Days and 1 Year – Transfemoral Access 
Study  
Device/N 
All-
cause 
Death  
Disabling
/ Major 
Stroke 
Major 
VC 
LT 
Bleeding  
AKI 
PPM 
PORTICO Pre-
CE Mark Studyf 
(2018)45 
Portico / 222† 
3.6 
3.2 
7.3 
3.6 
1.4e 
13.6 
LRT Trialf 
(2019)46 
SAPIEN 3 or 
CoreValvev / 200# 
0.0 
0.0 
3.0 
3.0l 
0.0e 
6.5 
UK & Ireland 
Implanters’ 
Registryw 
(2019)47 
Evolut 34mm / 217* 
3.2 
3.7 k 
2.3 
0.9 
0.9h 
15.7x 
EVOLUT R – 
Large Annuliy 
(2019)48 
Evolut 34mm / 35† 
CoreValve 31mm / 
71† 
0.0 
8.5 
0.0k 
1.4k 
0.0 
4.2 
2.9z 
19.6z 
0.0e 
5.3e 
5.7 
26.8 
TVT Registry – 
Large 
Annulusy,aa 
(2019)49 
Evolut R 34 / 1813‡ 
CoreValve 31 / 
1813‡ 
1.9 
2.2 
2.2k 
2.0k 
0.3 
0.5 
4.6l 
6.6l 
– 
– 
15.2bb 
23.3bb 
1-Year Outcomes – Randomized Studies 
PARTNER 1Aa 
(2011)19 
SAPIEN / 244† 
22.2 
3.8 
14.4 
16.2b 
5.1c 
5.5 
PARTNER 2Ad 
(2016)27 
SAPIEN XT / 775* 
10.0 
4.3 
8.8 
11.1 
2.2e 
9.6 
PARTNER 2Bf 
(2015)34 
SAPIEN XT / 284† 
SAPIEN / 276† 
22.3 
23.3 
4.8 
5.5 
10.3 
16.1 
14.1 
19.9 
31.0e 
31.3e 
8.1 
8.0 
PARTNER 3f 
(2019)29 
SAPIEN 3 / 496# 
1.0 
0.2 
2.8 
2.8 
– 
7.3 
CoreValve High 
Riski (2014)22 
CoreValve / 390† 
14.2 
5.8 
6.2 
16.6 
6.0g 
22.3 
NOTIONj 
(2015)35 
CoreValve / 142‡ 
4.9 
2.9k 
– 
– 
– 
38.0 
SURTAVIm 
(2017)28 
CoreValve / 864* 
6.7 
2.2 
– 
– 
– 
– 
CoreValve Low 
Riski (2019)30 
CoreValve, Evolut 
R, Evolut PRO / 
725# 
2.4 
0.8 
3.8 
3.2 
0.9h 
19.4 
CHOICEf 
(2015)50 
SAPIEN XT / 121† 
CoreValve / 117† 
17.4 
12.8 
5.8 
3.4 
11.6 
12.0 
14.0b 
12.8b 
– 
– 
23.4 
38.0 
REPRISE IIIf 
(2018)37 
Lotus Valven / 607† 
CoreValven / 305† 
11.9 
13.5 
3.6 
7.1 
7.7 
6.1 
9.9 
9.8 
2.6h 
3.7h 
34.2 
18.5 
PORTICO IDEo 
(2020)38 
Portico / 381† 
Commercial / 369† 
14.3 
12.0 
1.6 
2.9 
– 
– 
– 
– 
1-Year Outcomes – Single-Arm Studies 
PARTNER 
NRCAf (2014)39 
SAPIEN / 1023† 
19.0 
3.6 
8.4 
12.9b 
3.6e 
– 
CoreValve 
Extreme Riskq 
(2014)41 
CoreValve / 489† 
24.3 
4.3 
8.4 
17.6 
11.8 
26.2 

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Table 4.1-1: TAVR Outcomes at 30 Days and 1 Year – Transfemoral Access 
Study  
Device/N 
All-
cause 
Death  
Disabling
/ Major 
Stroke 
Major 
VC 
LT 
Bleeding  
AKI 
PPM 
SAPIEN 3cc 
(2016)51 
SAPIEN 3 / 925* 
6.5 
1.7 
– 
– 
– 
12.4 
PORTICO Pre-
CE Mark Studyf 
(2018)45 
Portico / 222† 
13.8 
5.8 
8.8 
5.2 
3.0 
14.7 
LRT Trialf 
(2019)46 
SAPIEN 3 or 
CoreValvev / 200# 
3.0 
0.0 
– 
– 
– 
7.3 
Data are presented as %; N is the number of subjects with transfemoral/iliofemoral access unless indicated otherwise; 
† = high/extreme surgical risk; * = intermediate surgical risk; # = low surgical risk; ‡ = all risk. 
The SAPIEN™, SAPIEN XT™, and SAPIEN 3™ Transcatheter Heart Valve Systems are manufactured by Edwards 
Lifesciences, Irvine, CA, USA. The CoreValve®, CoreValve Evolut™ R, and CoreValve Evolut™ PRO Transcatheter 
Aortic Valve Systems are manufactured by Medtronic Corp, Dublin, Ireland. The PORTICO™ Transcatheter Aortic 
Heart Valve Implantation System is manufactured by Abbott Structural Heart, St. Paul, MN, USA. The Lotus™ Valve 
System is manufactured by Boston Scientific Corporation, Marlborough, MA, USA. 
a: 
70% TF and 30% TA  
b: 
Major bleeding 
c: 
Renal replacement therapy 
d: 
76% TF and 24% TA  
e: 
AKIN Stage 3 (including renal replacement therapy) 
f: 
100% TF 
g: 
Modified RIFLE classification per VARC 1 
h: 
AKIN Stage 2 or 3 
i: 
83% TF and 17% TAo/SC for CoreValve High Risk; 99% TF and 1% Tao/SC for CoreValve Low Risk 
j: 
97% TF and 3% SC 
k: 
All stroke  
l: 
Life-threatening and major 
m: 94% TF, 4% TAo, and 2% SC 
n: 
Outcomes are for the implanted analysis sets: N=601 Lotus; N=303 CoreValve (153 CoreValve and 144 Evolut R) 
o: 
Portico: 94% TF, 4% TAo, 2% SC; Commercial (includes SAPIEN [1%], XT [7%], SAPIEN 3 [57%], CoreValve 
[4%], Evolut R [25%], Evolut PRO [6%]): 95% TF, 3% Tao, 1% SC, <1% TA 
p: 
87% TF and 13% TA/TAo (intermediate and high risk) 
q: 
99% TF (1% not implanted)  
r:  98% TF and 2% TAo 
s: 
95% TF and 5% TAx 
t: 
Includes patients who experienced pericardial tamponade  
u: 
90% TF and 10% other 
v: 
88% SAPIEN 3 and 12% CoreValve (CoreValve, Evolut R, or Evolut PRO) 
w: 91.2% TF, 7.4% SC, 1.4% TAo 
x: 
Excludes patients with PPM at baseline 
y: 
Outcomes at discharge/in-hospital 
z: 
All bleeding 
aa: Matched cohorts; CoreValve: 93.3% TF, 4.0% SC, 2.2% TAo and 94.7% extreme/high risk, 5.3% intermediate/low 
risk; Evolut R: 93.2% TF, 4.1% SC, 1.1% TAo and 78.6% extreme/high risk, 21.4% intermediate/low risk 
bb: PPM or implantable defibrillator 
cc: 88% TF and 12% TA/TAo 
Abbreviations: AKI=acute kidney injury; LT=life threatening; PPM=permanent pacemaker; PVR=paravalvular 
regurgitation; SC=subclavian; TA=transapical; TAo=trans-aortic; TAVR=transcatheter aortic valve replacement; 
TAx=transaxillary; TF=transfemoral/iliofemoral; VARC=Valve Academic Research Consortium; VC=vascular 
complications 

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Infrequent but significant complications that potentially impact long-term outcomes may 
limit the utility of TAVR52. Suboptimal valve deployment can result in embolization, the 
need for a second device, or coronary occlusion53. Valve malposition requiring a second 
TAVR valve at the initial procedure has been associated with increased procedural risk54. 
Placement in a heavily calcified native valve can produce an incomplete seal between the 
bioprosthetic valve and aortic annulus, resulting in paravalvular regurgitation (PVR), which 
in turn has been associated with increased mortality55-57. Iterative improvements in TAVR 
devices and periprocedural technique have reduced but not eliminated PVR44,51,58. The need 
for permanent pacemaker (PPM) implantation is another limitation of TAVR59-63. 
Newer-generation devices have aimed to address these limitations64. The ACURATE TA™ 
Aortic Bioprosthesis (Symetis SA, Ecublens, Switzerland) is a self-expandable nitinol TAVR 
stent housing a porcine bioprosthesis and placed in a supra-annular position via transapical 
delivery65. The device was designed to allow easy and intuitive implantation (single 
operator). The ACURATE neo™ Aortic Bioprosthesis was subsequently developed for 
transfemoral (TF) use with the ACURATE neo™ TF Delivery System. ACURATE neo has a 
pericardial skirt on the interior and exterior of the stent body which serves to limit PVR65.   
4.2. 
Study Rationale 
The ACURATE device potentially provides a number of performance and safety features 
beyond that of earlier TAVR devices. These include easy and intuitive delivery and valve 
implantation and a valve design intended to overcome high rates of post-interventional PPM 
implantation. The iterative ACURATE neo TF Aortic Bioprosthesis has a pericardial skirt on 
the interior and exterior of the stent body which serves to limit PVR. The subsequent 
ACURATE neo2 and ACURATE Prime Transfemoral Valve Systems were designed with 
improvements in the pericardial skirt and the delivery system.  
The anticipated risks and benefits known at the time this protocol was written and associated 
with the ACURATE Transfemoral Aortic Valve System and with participation in this clinical 
investigation are summarized in the Investigator Brochure (IB) and in Section 18 of this 
document. The conclusion of the risk-benefit analysis demonstrates that the known risks 
associated with the procedure, and specifically the use of the ACURATE Transfemoral 
Aortic Valve System, have been mitigated to acceptable limits. It was also concluded that the 
aforementioned design features may improve procedural safety and longer-term clinical 
outcomes. The available Sponsor-provided training program and proctorship for physicians 
(Section 16.4.2) further mitigates risk. The result is a procedure with residual subject risk 
comparable to that of currently available transcatheter aortic valves and potential benefit 
compared with other alternatives.  
It is therefore determined that: 
• All applicable risks have been addressed through appropriate testing and any residual 
risks are acceptable when weighed against the potential benefits to the subject. 
• The potential benefits of the use of the device out-weigh the risks. 

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Note: The term “ACURATE” is used generically and includes various iterations of the 
device.  
5. Device Description 
The study devices are intended to improve aortic valve function for subjects with severe 
native aortic stenosis who are indicated for TAVR. Every subject in the randomized cohort 
must be deemed treatable with an available size of both the test and the control device. The 
control device in the planned size must be approved for treatment of the subject and 
commercially available at the investigational center where the implant procedure is being 
performed. 
5.1. 
ACURATE Transfemoral Aortic Valve System (Test) 
The investigational device (ACURATE Transfemoral Aortic Valve System [ACURATE]) is 
designed by Boston Scientific Corporation, Marlborough, MA, USA. It is composed of 
separately packaged components as listed below. 
• A single use aortic valve, the ACURATE neo2™ Aortic Valve (valve sizes S, M, and 
L) or the ACURATE Prime™ Aortic Valve (valve size XL)  
• A single use transfemoral delivery system, the ACURATE neo2™ Transfemoral 
Delivery System (for use with valve sizes S, M, and L) or the ACURATE Prime 
Transfemoral Delivery System (for use with valve size XL) 
Note: The single use ACURATE neo2™ Loading Kit is packaged with the ACURATE 
neo2™ Transfemoral Delivery System. 
• A single use loading kit, ACURATE Prime™ Loading Kit XL (to allow loading of the 
XL valve onto the delivery system) 
Valves are manufactured in Belo Horizonte, Brazil. Delivery systems and loading kits are 
manufactured in Ecublens, Switzerland and/or Galway, Ireland. All components are 
investigational and are labeled as such. The device components are described briefly below. 
Additional information is provided in the ACURATE neo2 and ACURATE Prime Clinical 
Directions/Instructions for Use (DFU/IFU) and the IB. 
Note: Throughout this document DFU and IFU are used interchangeably. 
5.1.1. 
ACURATE neo2™ Aortic Valve and ACURATE Prime™ Aortic Valve XL 
The ACURATE neo2 Aortic Valve is an iteration of the CE Mark-approved 
ACURATE neo™ Aortic Bioprosthesis (Boston Scientific Corporation, Marlborough, MA, 
USA). The ACURATE Prime Aortic Valve XL is an iteration of the CE Mark-approved 
ACURATE neo2 Aortic Valve. There are 3 valve sizes of ACURATE neo2 (Small, Medium, 
and Large) and 1 valve size of ACURATE Prime (Extra Large). Table 5.1-1 shows the 
sizing chart used for the ACURATE IDE Roll-In Cohort, Main Randomized Cohort, and 
ACURATE Prime XL Nested Registry. Table 5.1-2 shows the sizing chart for the Extended 

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Durability Study and the Continued Access Study. Please see Section 7.1 below for study 
cohort descriptions. 
Note: ACURATE Prime™ XL is only available in the United States. 
Table 5.1-1: ACURATE neo2 and ACURATE Prime Aortic Valve Size Chart – Main 
Randomized Cohort, Roll-In Cohort and ACURATE Prime XL Nested Registry 
Sizea 
Nominal Diameter at Waist Level 
Aortic Annulus Size  
Small (S) 
23 mm 
21 mm ≤ native annulus diameter ≤ 23 mm 
Medium (M) 
25 mm 
23 mm < native annulus diameter ≤ 25 mm 
Large (L) 
27 mm 
25 mm < native annulus diameter ≤ 27 mm 
Extra Large (XL)b 
29 mm 
26.5 mm < native annulus diameter ≤ 29 mm 
a: ACURATE neo2™ available in sizes S, M, L and ACURATE Prime™ available in size XL 
b: ACURATE Prime™ XL is only available in the United States. 
 
Table 5.1-2: ACURATE neo2 and ACURATE Prime Aortic Valve Size Chart – 
Extended Durability Study and Continued Access Study 
Sizea 
Nominal Diameter at Waist Level 
Aortic Annulus Size  
Small (S) 
23 mm 
20.5 mm ≤ native annulus diameter ≤ 23 mm 
Medium (M) 
25 mm 
22.5 mm < native annulus diameter ≤ 25 mm 
Large (L) 
27 mm 
24.5 mm < native annulus diameter ≤ 27mm 
Extra Large (XL)b 
29 mm 
26.5 mm < native annulus diameter ≤ 29 mm 
a: ACURATE neo2™ available in sizes S, M, L and ACURATE Prime™ available in size XL 
b: ACURATE Prime™ XL is only available in the United States. 
 
The valves are shown in Figure 5.1-1 (ACURATE neo2 Aortic Valve in Panel A and 
ACURATE Prime Aortic Valve XL in Panel B). Each valve consists of three porcine 
pericardial tissue leaflets, a self-expandable nitinol stent acting as an anchoring structure 
within the native aortic annulus for the porcine pericardium valve that is sutured onto it, and 
a double porcine pericardium skirt sutured on the inner and outer surface of the stent to 
minimize PVR. The valve is deployed from top to bottom, unsheathing first the upper crown, 
then the stabilization arches. The valve is designed so that in the final step the lower crown 
can be deployed to anchor the device with minimal protrusion into the left ventricular 
outflow tract. The top-down implantation technique provides predictable positioning and 
hemodynamic stability. The ACURATE neo2 design iteration includes an advanced sealing 
technology intended to limit further the extent of PVR. The ACURATE Prime Aortic Valve 
XL iteration allows easier removal of a fully loaded valve and has optimized radial force 
with the addition of connected links. The valve is intended as a permanently implanted 
device. 

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Figure 5.1-1: ACURATE Aortic Valve 
A: ACURATE neo2 Aortic Valve; B: ACURATE Prime Aortic Valve XL 

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5.1.2. 
ACURATE neo2 Transfemoral Delivery System and ACURATE Prime 
Transfemoral Delivery System XL 
The ACURATE neo2 Transfemoral Delivery System and ACURATE Prime Transfemoral 
Delivery System XL are transfemoral delivery systems for the guidance and placement of the 
valve implant.  
ACURATE neo2 is a slightly modified version of the CE Mark-approved ACURATE TF™ 
Transfemoral Delivery System (Boston Scientific Corporation, Marlborough, MA, USA). 
Figure 5.1-2 shows an overview of the system and Figure 5.1-3 shows a close-up of the 
distal end. An insertion aid shown in Figure 5.1-4 facilitates insertion of the delivery system 
into a compatible introducer sheath (see Section 5.1.3 below). The ACURATE neo2 Aortic 
Valve is loaded onto the delivery system prior to use. 
 
Figure 5.1-2: ACURATE neo2 Transfemoral Delivery System – Overview 
 
 
Figure 5.1-3: ACURATE neo2 Transfemoral Delivery System – Distal End 
 
Capsule
Tip
Stent holder 
with self-expandable cage
Middle member
Outer member
Shuttle
with soft tip
Markerband
Inner member

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Figure 5.1-4: Insertion Aid Positioned over the Delivery System 
 
The ACURATE Prime Transfemoral Delivery System XL is a slightly modified version of 
the ACURATE neo2 Transfemoral Delivery System. The system is compatible with the 14F 
iSLEEVE introducer (see Section 5.1.3 below) and has a new distal release mechanism to 
allow quicker final valve release and improved valve detachment. Figure 5.1-5 shows an 
overview of the system and Figure 5.1-6 shows a close-up of the distal end. Prior to use, the 
ACURATE Prime Aortic Valve XL is loaded onto the delivery system with the 
investigational ACURATE Prime Loading Kit XL.  
 
Figure 5.1-5: ACURATE Prime™ Transfemoral Delivery System XL – Overview 
 
 
 
Figure 5.1-6: ACURATE Prime™ Transfemoral Delivery System XL – Distal End with 
Loaded ACURATE Prime™ Aortic Valve XL 
 

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The delivery systems are single-use catheters. Please see Section 10.7.2.2 for additional 
information on preparing and using the investigational devices. Please see Section 5.1.3 
regarding the recommended introducer set. 
Only BSC authorized and trained personnel may load the ACURATE Aortic Valve. 
5.1.3. 
Introducer Set 
The commercially available 14F iSLEEVE™ Introducer Set (iSLEEVE; Boston Scientific 
Corporation, Marlborough, MA, USA) shall be used as an accessory to the ACURATE neo2 
Transfemoral Aortic Valve System and the ACURATE Prime Transfemoral Aortic Valve 
System during the procedure. The iSLEEVE is composed of a dilator and an introducer 
sheath manufactured with materials commonly used in medical devices having contact with 
circulating blood. It has a hydrophilic coating that upon activation increases the lubricity of 
the surface to aid in delivery. The sheath component of the iSLEEVE is expandable, which 
allows for transient sheath expansion during delivery system introduction. The 14F iSLEEVE 
is suitable for use in subjects with femoral vascular access ≥5.5 mm. 
Note: In countries where the iSLEEVE is approved, the commercial device will be used. It 
will be considered an investigational device in countries where it is not approved.  
5.2. 
Control Device 
The control device is a commercially available balloon-expandable SAPIEN 3™ 
Transcatheter Heart Valve or future iteration (SAPIEN 3; Edwards Lifesciences LLC, Irvine, 
CA, USA) or a commercially available self-expanding CoreValve® Transcatheter Aortic 
Valve Replacement System, CoreValve® Evolut™ R Recapturable TAVR System, 
EVOLUT™ PRO System, or future iteration (CoreValve; Medtronic, Inc., Dublin, Ireland) 
TAVR device that is introduced via the femoral artery using conventional catheterization 
techniques and is approved for risk profiles included in this study. The associated DFUs 
should be consulted to determine the appropriate control valve sizes required to treat subjects 
with a native annulus diameter range between 20.5mm and 29mm. 
Note: Every subject in the Main Randomized Cohort and the Extended Durability Study 
must be deemed treatable with an available size of both the test (ACURATE) device and the 
control device. The control device in the planned size must be approved for treatment of the 
subject (e.g., if a subject to be treated is considered to be at intermediate surgical risk, then 
the planned control device must be approved for use in intermediate-risk subjects). The 
control device in the planned size must be commercially available at the investigative center 
where the implant procedure is being performed. 
5.3. Device Labeling 
5.3.1. Test Device 
The study Manual of Operations includes the DFU/IFU for the ACURATE neo2 Valve, 
ACURATE neo2 Transfemoral Delivery System, ACURATE Prime Aortic Valve, 

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ACURATE Prime Transfemoral Delivery System, and ACURATE Prime Loading Kit. 
Study devices are labeled on the top and one side (one label wraps around the top and side) 
of the outer carton and on the sterile pouch. Packaging will include peelable, self-adhesive 
labels for each unit shipped. The labeling will include the following information. 
• Product Name 
• Unique Identifier or Lot Number/Serial Number  
• Expiration (use by) date (labeled as month/year, device not to be used after the last day 
of the indicated month) 
The following statement appears on the label.  
Caution: Investigational Device. Limited by United States law to investigational use. 
Exclusively for Clinical Investigations. 
In addition, the following statement appears on the product labeling. 
Investigational Device. To be Used by Qualified Investigators only.     
5.3.2. Control Device 
Information is provided in the DFU/IFU supplied with the commercially available TAVR 
devices used as the control device in this study. 
6. Study Objectives and Endpoints 
6.1. 
Study Objectives 
The objective of the ACURATE IDE clinical study is to evaluate safety and effectiveness of 
the ACURATE Transfemoral Aortic Valve System for TAVR in subjects with severe native 
aortic stenosis who are indicated for transcatheter aortic valve replacement. 
6.2. 
Study Endpoints 
Outcomes in the randomized cohorts of the ACURATE IDE trial (Main Randomized Cohort 
and Extended Durability Study) will be assessed on an intention-to-treat (ITT) basis and an 
implanted basis. The ITT analysis populations of the ACURATE IDE randomized cohorts 
include subjects who sign an Informed Consent Form (see Section 20), are enrolled in the 
trial (see Section 9.1 for point of enrollment), and are randomized, whether or not an 
assigned study device is implanted. The implanted analysis populations of the ACURATE 
IDE randomized cohorts include ITT subjects who are implanted with the assigned (test 
versus control), randomized study device. For the implanted randomized cohort analysis sets, 
if a subject receives 2 different valve types from 2 different manufacturers, the subject will 
be excluded from the implanted analysis. 
Among the Roll-In, ACURATE Prime XL, and CAS cohorts of ACURATE IDE, all subjects 
who sign the IRB-approved study ICF and are enrolled in the trial will be included in the 

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analysis sample, regardless of whether the study device was implanted. Endpoint definitions 
can be found in Table 25.2-1. 
6.3. Primary Endpoint 
The primary endpoint is a composite of all-cause mortality, all stroke, and rehospitalization 
at 1 year. The primary analysis set for the primary endpoint for the Main Randomized Cohort 
is the ITT analysis set.  
Note: For the primary endpoint, rehospitalization includes hospitalization for valve-related 
symptoms or worsening congestive heart failure (NYHA class III or IV); per VARC-2 
definition.  
6.4. Additional Measurements 
This section describes required assessments to be performed in the ACURATE IDE trial.  
Additional measurements based on the VARC endpoints and definitions66-68 (see Note 1 
below) will be collected peri- and post-procedure, at discharge or 7 days post-procedure 
(whichever comes first), 30 days, 6 months, and annually up to 10 years post index 
procedure, unless otherwise specified below.  
• Safety endpoints adjudicated by an independent Clinical Events Committee (CEC; 
Section 21.1.1): 
o Mortality: all-cause, cardiovascular, and non-cardiovascular 
o Stroke: disabling and non-disabling 
o Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and 
spontaneous (>72 hours post index procedure) 
o Bleeding: life-threatening (or disabling) and major (through 5 years) 
o Acute kidney injury (AKI; ≤7 days post index procedure): based on the AKIN 
System69,70 Stage 3 (including renal replacement therapy) or Stage 2 
o Major vascular complications (through 5 years) 
o Repeat procedure for valve-related dysfunction (surgical or interventional therapy) 
o Hospitalization for valve-related symptoms or worsening congestive heart failure 
(NYHA class III or IV) 
o New permanent pacemaker implantation resulting from new or worsened conduction 
disturbances (definitions in Table 25.2-1)  
o New onset of atrial fibrillation or atrial flutter 
o Coronary obstruction: periprocedural (≤72 hours post index procedure) 
o Ventricular septal perforation: periprocedural (≤72 hours post index procedure) 
o Mitral apparatus damage: periprocedural (≤72 hours post index procedure) 
o Cardiac tamponade: periprocedural (≤72 hours post index procedure) 
o Valve migration 

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o Valve embolization 
o Ectopic valve deployment 
o Transcatheter aortic valve (TAV)-in-TAV deployment  
o Prosthetic aortic valve thrombosis 
o Prosthetic aortic valve endocarditis 
• Device performance endpoints peri- and post-procedure:  
o Successful vascular access, delivery and deployment of the study valve and 
successful retrieval of the delivery system 
o Grade of aortic valve regurgitation: paravalvular, central and combined  
• Device success, defined as absence of procedural mortality, correct positioning of a 
single transcatheter valve in the proper anatomical location, and intended performance 
of the study device (indexed effective orifice area [iEOA] >0.85 cm2/m2 for BMI 
<30 kg/m2 and iEOA >0.70 cm2/m2 for BMI ≥30 kg/m2 plus either a mean aortic valve 
gradient <20 mm Hg or a peak velocity < 3m/sec, and no moderate or severe prosthetic 
valve aortic regurgitation) 
• Additional indications of prosthetic aortic valve performance as measured by 
transthoracic echocardiography (TTE; see Note 2 and Note 3 below) and assessed by an 
independent core laboratory, including EOA, mean and peak aortic gradients, peak 
aortic velocity, and grade of aortic regurgitation 
• Functional status as evaluated by New York Heart Association (NYHA) classification 
(see Note 3 below) 
• Neurological status (see Note 4 below) as determined by the following: 
o National Institutes of Health Stroke Scale (NIHSS) conducted by a neurology 
professional or certified personnel at discharge and 1 year  
o Modified Rankin Scale (mRS) conducted by a neurology professional or certified 
personnel at discharge and all follow-up visits up to 5 years 
o Neurological physical exam conducted by a neurologist, neurology fellow, 
neurology physician assistant, or neurology nurse practitioner in all subjects where 
stroke is suspected 
• Health status as evaluated by Kansas City Cardiomyopathy71 and SF-1272 Quality of 
Life (QOL) questionnaires at baseline, 1 month, 1 year, and 5 years. 
• For subjects in the 4D CT Imaging Substudy, assessments using 4D CT at 30 days and 
1 year will be done as listed below (see Note 5 below).  
o Assessment of leaflet mobility 
o Assessment of hypoattenuated leaflet thickening (HALT73) 
o Assessment of leaflet thrombosis 
Note 1: The most current VARC definitions and endpoints available at the beginning of the 
trial were used. 

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Note 2: In ACURATE IDE, at least 1 post-procedural echocardiogram must be obtained 
before discharge or 7 days (whichever comes first); if multiple echocardiographic studies are 
performed prior to discharge and within 7 days of the procedure, the latest study performed 
will be used for analysis. 
Note 3: Echocardiography and NYHA assessment are not required in years 6, 8, and 9 
(telephone follow-up only). 
Note 4: Table 6.4-1 summarizes actions required for subjects with a neurological event in 
ACURATE IDE. 
Table 6.4-1: Neurological Events in ACURATE IDE 
Subject Status  
Action  
Subjects who receive a study device (test or control) 
and are diagnosed with a stroke 
A neurological physical exam (conducted by a 
neurologist, neurology fellow, neurology physician 
assistant, or neurology nurse practitioner), NIHSS 
assessment (conducted by a neurology professional 
or certified personnel), and mRS (conducted by a 
neurology professional or certified personnel) must 
be performed after the event. Additionally, mRS 
must be administered at 90±14 days after a stroke 
(see Table 10.1-1). The simplified mRS 
questionnaire may be used for the follow-up 
assessment. 
Subjects who receive a study device (test or control) 
and are diagnosed with a transient ischemic attack 
mRS must be performed after the event. 
- Subjects with an attempted procedure but no 
implanted study device (test or control) who 
experience a neurological event within the first 
1 year after the index procedure 
- Randomized subjects with no index procedure 
who experience a neurological event within the 
first 1 year after randomization 
mRS must be performed after the event; mRS must 
also be administered at 90±14 days after a stroke and 
the results must be reported to the Sponsor. 
Abbreviations: mRS=modified Rankin Scale; NIHSS=National Institutes of Health Stroke Scale 
 
Note 5: Images will be read in a standard fashion for cardiac and non-cardiac findings by the 
clinical center CT imaging specialist. Clinical guidelines support anticoagulation with 
warfarin or another vitamin K inhibitor as a Class I recommendation for patients with 
established valve thrombosis4,5. However, there is no established guidance for 
pharmaceutical management of subclinical leaflet thrombosis. If deterioration of subject 
health due to suspected thrombosis occurs, the clinical center may request an unblinding of 
the Core Laboratory findings. 
6.5. 
Overview of Objectives and Endpoints 
Table 6.5-1 provides an overview of the aforementioned study objectives and endpoints and 
a justification for the specific endpoints. 

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Table 6.5-1: Overview of Objectives and Endpoints 
Objective 
Endpoint 
Rationale for Endpoint 
Primary Safety and Effectiveness 
 
Determine safety 
and effectiveness 
of the valve 
implant 
1-Year Composite: mortality, all 
stroke, and rehospitalization  
Assess the long-term benefit (1 year) in a large 
elderly population receiving ACURATE neo2; 
assessments recommended by VARC66,67. 
Events are adjudicated by an independent CEC.  
Additional Measurements of Safety and Effectiveness 
 
Evaluate safety 
of the valve 
implant and the 
procedure 
Safety measures at discharge, 
30 days, 6 months, and annually 
up to 10 years post index 
procedure 
Safety assessments recommended by VARC66,67 
for this elderly population. 
Events are adjudicated by an independent CEC. 
 
Evaluate 
effectiveness of 
the valve implant  
Effectiveness measures at 
discharge, 30 days, 6 months, and 
annually up to 10 years post index 
procedure 
Effectiveness assessments recommended by 
VARC66,67 for this elderly population. 
Events are adjudicated by an independent CEC.  
Abbreviations: CEC=Clinical Events Committee; VARC=Valve Academic Research Consortium 
 
7. Study Design 
ACURATE IDE is a prospective, multicenter trial designed to evaluate the safety and 
effectiveness of the ACURATE Transfemoral Aortic Valve System (ACURATE) for TAVR 
in subjects with severe native aortic stenosis who are indicated for transcatheter aortic valve 
replacement.  
7.1. 
Scale and Duration 
Subjects will be enrolled at up to 85 centers in the United States, Canada, Australia, and 
Europe. There will be up to 2820 subjects total in ACURATE IDE. It is expected that >80% 
of enrolled subjects will be from the United States. To achieve sufficient distribution of 
lower risk subjects in the Main Randomized Cohort, there will be ≥ 30% intermediate risk 
randomized subjects and ≥ 35% low risk randomized subjects enrolled (please see definition 
of operative risk in Section 25.2).  
The ACURATE IDE study cohorts include the following. 
• Main Randomized Cohort: A prospective, multicenter, 1:1 randomized controlled trial 
(RCT; ACURATE versus a commercially available balloon-expandable SAPIEN 3™ 
Transcatheter Heart Valve or future iteration [SAPIEN 3; Edwards Lifesciences LLC, 
Irvine, CA, USA] or a commercially available self-expanding CoreValve® Transcatheter 
Aortic Valve Replacement System, CoreValve® Evolut™ R Recapturable TAVR 
System, EVOLUT™ PRO System, or future iteration [CoreValve; Medtronic, Inc., 
Dublin, Ireland]). There will be 1500 subjects in the RCT.    
• Roll-In Cohort: A non-randomized Roll-In phase with the test device. Centers that do 
not have implantation experience with the ACURATE neo™ bioprosthesis 

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(transfemoral delivery) will perform at least 2 Roll-In cases with ACURATE neo2 
before commencing treatment in the Main Randomized Cohort (up to 170 Roll-In 
subjects in total). Centers with prior experience with ACURATE are not required to do 
Roll-In cases. Data from Roll-In subjects will be summarized separately from the Main 
Randomized Cohort and will not be included in the primary endpoint analysis. 
• 4D CT Imaging Substudy: Select centers with the ability to perform high quality 4D 
computed tomography (CT) scans will include subjects (minimum of 200) from the 
Main Randomized Cohort in a 4D CT Imaging Substudy to assess the prevalence of 
reduced leaflet mobility and hypoattenuated leaflet thickening (HALT)73 and the 
relationship, if any, to clinical events. Centers should ask all eligible subjects to consider 
participation in the substudy. 
• ACURATE Prime™ XL Nested Registry: A non-randomized, nested registry cohort 
of subjects who will receive the ACURATE Prime™ Transfemoral Aortic Valve 
System XL (ACURATE Prime XL Nested Registry). Participating centers will be a 
subset of United States centers that have enrolled subjects in ACURATE IDE. Data 
from subjects in this nested registry will be summarized separately from the randomized, 
Roll-In, and Continued Access Study cohorts. There will be 50 subjects at up to 20 
centers in the United States enrolled in this registry. 
• ACURATE Extended Durability Study: An additional 1:1 randomized study 
(ACURATE versus Control [commercially available SAPIEN 3 or CoreValve] TAVR 
device) including only subjects considered to be at low surgical risk. Subjects will 
receive ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime XL. 
Randomization will be stratified by center and by intended control device. Low-risk 
subjects receiving ACURATE neo2 will be enrolled in the Extended Durability Study 
only after enrollment of the Main Randomized Cohort is completed. Enrollment of low-
risk subjects with ACURATE Prime XL will start after enrollment in both the Main 
Randomized Cohort and the ACURATE Prime XL Nested Registry is completed. Data 
from subjects in the Extended Durability Study will be summarized separately from 
other cohorts. 
Note: Centers must complete the roll-in phase of the study, if applicable, before 
participating in ACURATE Extended Durability Study. 
• ACURATE Continued Access Study (CAS): An additional cohort of subjects 
receiving ACURATE neo2 (S, M, and L valve sizes) or ACURATE Prime XL. 
Enrollment of subjects with ACURATE neo2 will start after enrollment of the 
ACURATE IDE Main Randomized Cohort is completed. Enrollment of subjects with 
ACURATE Prime XL will start after enrollment in both the Main Randomized Cohort 
and the ACURATE Prime XL Nested Registry is completed. Subjects at all surgical 
risks may be enrolled in ACURATE CAS, but low-risk subjects will be considered for 
enrollment only after enrollment in the Extended Durability Study is completed. Data 
from subjects in ACURATE CAS will be summarized separately from other cohorts 
and will be used to further assess performance and safety. 

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Note: Centers must complete the roll-in phase of the study, if applicable, before 
participating in ACURATE CAS. 
The devices to be used and the subject risk levels for the ACURATE IDE cohorts are 
summarized below in Table 7.1-1.  
Table 7.1-1: Devices and Risk Levels for ACURATE IDE Cohorts 
Device 
Cohort 
Roll-In 
Main RCT 
Prime XL 
Nested 
Registry 
Extended 
Durability1 
Continued 
Access 
Study1 
ACURATE neo2 (S, M, L) 
All risks 
All risks 
N/A 
Low risk 
All risks2 
ACURATE Prime (XL) 
N/A 
N/A 
All risks 
Low risk3 
All risks2,3 
Note 1: Enrollment of subjects in the Extended Durability cohort and the CAS cohort will begin after 
completion of enrollment in the Main RCT. 
Note 2: Enrollment of low-surgical-risk subjects in the CAS cohort will begin after completion of enrollment 
the Extended Durability cohort. 
Note 3: Enrollment of subjects receiving ACURATE Prime XL in the Extended Durability and CAS cohorts 
will begin after enrollment completion in both the Main RCT and Prime XL Nested Registry. 
Abbreviations: CAS=Continued Access Study; N/A=not applicable; RCT=randomized controlled trial 
 
All subjects implanted will be followed at baseline, peri- and post-procedure, at discharge or 
7 days post-procedure (whichever comes first), 30 days, 6 months, and then annually for up 
to 10 years post-procedure. Enrollment is expected to be completed in approximately 
62 months; therefore, the total study duration is estimated to be approximately 16 years. The 
study duration for each subject is expected to be approximately 10 years. Implanted subjects 
participating in the 4D CT Imaging Substudy will undergo additional 4D CT assessment at 
30 days and 1 year. Enrolled subjects who do not have a study device implanted will be 
assessed through 1-year post-procedure for safety/adverse events.   
The study design is summarized below in Figure 7.1-1. As noted above, enrollment in the 
Extended Durability Study will commence for low-risk subjects receiving ACURATE neo2 
after enrollment of the Main Randomized Cohort is completed. Enrollment of low-risk 
subjects receiving ACURATE neo2 in ACURATE CAS will begin after enrollment in the 
Extended Durability Study is completed. Enrollment of low-risk subjects with ACURATE 
Prime XL will start after enrollment in both the Main Randomized Cohort and the 
ACURATE Prime XL Nested Registry is completed.  

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Figure 7.1-1: ACURATE IDE Study Design 
The ACURATE IDE study will be conducted in accordance with 21 CFR Parts 11, 50, and 
54; the relevant parts of the International Conference on Harmonisation (ICH) Guidelines for 
Good Clinical Practices (GCP); the International Standard ISO 14155 Clinical Investigation 
of Medical Devices for Human Subjects–Good Clinical Practice; ethical principles that have 
their origins in the Declaration of Helsinki; and pertinent individual country/state/local laws 
and regulations. The study shall not begin until the required approval/favorable opinion from 
the Institutional Review Board/Research Ethics Board/Human Research Ethics Committee/ 
Independent Ethics Committee (IRB/REB/HREC/IEC) and/or regulatory authority has been 
obtained, if appropriate. See Section 10 below for additional information on study design and 
data collection.  
The ACURATE IDE study is registered at ClinicalTrials.gov (NCT03735667).   
7.2. 
Treatment Assignment 
Screening materials from eligible subjects who provide written informed consent and who 
are identified by the investigators as having met all the inclusion and none of the exclusion 
criteria (see below Table 8.2-1 and Table 8.3-1, respectively) will be reviewed by a Case 

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Review Committee (CRC; see Section 21.2) to assess and confirm suitability of subjects for 
enrollment.  
For the randomized cohorts (Main Randomized Cohort and Extended Durability Cohort), 
eligible subjects will be randomized in a 1:1 allocation to receive either the test device 
(ACURATE; see Section 5.1) or a control device (SAPIEN 3 or CoreValve; see Section 5.2). 
The randomization schedules will be computer-generated, using a pseudo-random number 
generator. Randomization will be stratified by center and by intended control device. All 
randomized subjects will have unique identification numbers. Random permuted blocks will 
be employed to ensure approximate balance of treatment allocation within each stratum. 
Instructions on randomization are provided in the Manual of Operations. Subjects should be 
randomized within 7 calendar days of CRC approval. Subjects should be treated within 14 
calendar days after randomization. Because this is an unblinded study design, physician 
operators will not be blinded with respect to valve type implanted. 
Subjects in the non-randomized ACURATE Prime XL Nested Registry cohort will all 
receive ACURATE Prime™ Transfemoral Aortic Valve System XL valves. Subjects in the 
non-randomized ACURATE CAS will receive ACURATE neo2 (S, M or L) or ACURATE 
Prime XL valves. 
Note 1: Centers that do not have implantation experience with the ACURATE neo™ 
bioprosthesis (transfemoral delivery) will perform at least 2 non-randomized Roll-In cases 
before commencing treatment in the Main Randomized Cohort. Centers with prior 
ACURATE neo™ experience may do Roll-In cases but are not required to do so. All Roll-In 
subjects will have unique identification numbers.  
Note 2: Subjects in the Roll-In cohort (Section 9.1.1) and Main Randomized Cohort 
(Section 9.1.2) will have a documented aortic annulus size of ≥21mm and ≤27mm based on 
pre-procedure diagnostic imaging (see Table 5.1-1). Subjects in the ACURATE Prime XL 
Nested Registry (Section 9.1.3) will have a documented aortic annulus size of ≥26.5mm and 
≤29mm based on pre-procedure diagnostic imaging (see Table 5.1-1). Subjects in the 
Extended Durability Study (Section 9.1.4)  and the Continued Access Study (Section 9.1.5) 
will have a documented aortic annulus size of ≥20.5mm and ≤29mm based on pre-procedure 
diagnostic imaging (see Table 5.1-2). 
7.2.1. 
Treatment and Control 
Treatment and control devices are described briefly in Table 7.2-1. Please see Section 5 for 
the investigational device matrix and additional device information. 
Table 7.2-1: Treatment and Control Devices 
Treatment 
Device Name 
Device Description 
Test Device 
ACURATE 
ACURATE neo2™ Aortic Valve 
Valve size: 
 - S (small) 
 - M (medium) 
 - L (Large) 
Valve (additional information in Section 5.1.1) 
Includes 3 main components: 
- A three-leaflet porcine pericardial 
bioprosthetic aortic valve; 
- A self-expandable Nitinol stent; 

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Table 7.2-1: Treatment and Control Devices 
Treatment 
Device Name 
Device Description 
Nominal diameter at waist level is 23mm, 
25mm, and 27mm for the small, medium, 
and large valve diameters, respectively. 
ACURATE Prime™ Aortic Valve XL 
Valve size: 
 
- XL (extra-large) 
Nominal diameter is 29mm at waist level. 
ACURATE neo2™ Transfemoral 
Delivery System 
The delivery system is compatible with 
the S, M, and L valve sizes.  
ACURATE Prime™ Transfemoral 
Delivery System XL 
The delivery system is compatible with 
the XL valve size. 
ACURATE Prime™ Loading Kit XL 
- A double porcine pericardium skirt sutured on 
the inner and outer surface of the stent to prevent 
paravalvular leaks. 
Introduced via the iliofemoral artery. 
 
 
 
Delivery System (additional information in 
Section 5.1.2) 
Allows positioning and delivery of the 
transcatheter valve via iliofemoral access. 
 
 
 
Allows loading of the XL valve onto the 
compatible delivery system. 
Control 
Device 
SAPIEN 3*; 
CoreValve* 
Commercial TAVR device introduced via 
the femoral artery 
Balloon-expandable SAPIEN 3 or self-
expanding CoreValve TAVR device (see 
descriptions in Section 5.2) that is commercially 
available in the applicable region.  
Note: Every subject in the randomized cohort must be deemed treatable with an available size of both the test 
device and the control device. The control device in the planned size must be approved for treatment of the 
subject (i.e., if a subject to be treated is considered intermediate surgical risk, then the planned control device 
must be approved for use in intermediate-risk subjects). The control device in the planned size must be 
commercially available at the investigative center where the implant procedure is being performed. 
* Or future iteration 
Abbreviation: TAVR=transcatheter aortic valve replacement 
7.3. 
Justification for the Study Design 
There will be up to 2820 subjects total in ACURATE IDE. In order to support the stated 
objectives of this study (see Section 6.1) while also limiting the potential exposure of study 
subjects to risk, up to 170 subjects will be enrolled in the Roll-In phase of this study (centers 
without implantation experience with the ACURATE neo™ bioprosthesis [transfemoral 
delivery] are required to do 2 Roll-In cases each), 1500 subjects will be randomized and 
enrolled in the Main Randomized Cohort, 50 subjects will be enrolled in the ACURATE 
Prime XL Nested Registry at a subset of U.S. centers, a minimum of 100 subjects will be 
randomized in the Extended Durability Study, and up to 1000 subjects will be enrolled in the 
ACURATE Continued Access Study. Up to 85 centers in the United States, Canada, 
Australia, and Europe will participate in the study. Safety and effectiveness results will be 
reported on all enrolled subjects (see Section 19 for information on safety reporting). 
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from the Main Randomized Cohort in a 4D CT Imaging Substudy to assess the prevalence of 
reduced leaflet mobility and HALT73 and their relationship, if any, to clinical events. In 
addition to the risk-benefit analysis noted in Section 4.2 (see also Section 18), ongoing 
dynamic data safety monitoring will be performed throughout the trial to minimize risk to 
subjects (see Section 21.1). All implanted subjects will be followed for up to 10 years post 
index procedure. To achieve sufficient distribution of lower risk subjects, there will be ≥ 30% 
intermediate risk and ≥ 35% low risk subjects enrolled in the Main Randomized Cohort. Per 
society guidelines4,5 antiplatelet therapy with aspirin and/or a P2Y12 inhibitor is 
recommended after TAVR to decrease the risk of thrombotic or thromboembolic 
complications if there are no contraindications to these medications. 
8. Subject Selection  
8.1. 
Study Population and Eligibility  
Inclusion and Exclusion criteria are listed below in Section 8.2 and Section 8.3, respectively. 
8.2. 
Inclusion Criteria 
Subjects who meet all criteria in Table 8.2-1 may be given consideration for inclusion in this 
clinical investigation, provided no exclusion criterion (see Section 8.3) is met. Centers 
participating in the 4D CT Imaging Substudy must have the ability to perform high quality 
4D CT scans; subjects in this substudy must meet none of the additional exclusion criteria 
listed in Table 8.3-2. 
Table 8.2-1: ACURATE IDE Inclusion Criteria 
IC1.   
Subject has documented severe symptomatic native aortic stenosis defined as follows: aortic valve 
area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mmHg, OR 
maximal aortic valve velocity ≥4.0 m/s, OR Doppler velocity index ≤0.25 as measured by 
echocardiography and/or invasive hemodynamics76. 
Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection 
fraction <50%), dobutamine can be used to assess the grade of aortic stenosis (maximum 
dobutamine dose of 20 mcg/kg/min recommended)76; the subject may be enrolled if 
echocardiographic criteria are met with this augmentation. 
IC2. 
Subject has a documented aortic annulus size of ≥20.5 mm and ≤29 mm based on the center’s 
assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee 
[CRC]) and, for the Main Randomized Cohort and Extended Durability Study, is deemed treatable 
with an available size of both test and control device. 
IC3. 
For subjects with symptomatic aortic valve stenosis per IC1 definition above, functional status is 
NYHA Functional Class ≥ II. 
IC4. 
Heart team (which must include an experienced cardiac interventionalist and an experienced cardiac 
surgeon) agrees that the subject is indicated for TAVR, is likely to benefit from valve replacement, 
and TAVR is appropriate.  
IC5. 
Subject (or legal representative) understands the study requirements and the treatment procedures 
and provides written informed consent. 

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Table 8.2-1: ACURATE IDE Inclusion Criteria 
IC6. 
Subject, family member, and/or legal representative agree(s) and subject is capable of returning to 
the study hospital for all required scheduled follow up visits. 
IC7. 
Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy. 
Abbreviations: AVA=aortic valve area; CRC=Case Review Committee; NYHA=New York Heart 
Association; STS=Society of Thoracic Surgeons; TAVR=transcatheter aortic valve replacement 
 
8.3. 
Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8.3-1) cannot be included in this 
clinical study or will be excluded from this clinical study. No vulnerable populations will be 
enrolled in this study. See Section 25.2 for the definition of a vulnerable subject.   
Table 8.3-1: ACURATE IDE Exclusion Criteria 
EC1. 
Subject has a unicuspid or bicuspid aortic valve. 
EC2. 
Subject has had an acute myocardial infarction within 30 days prior to the index procedure (defined 
as Q-wave MI or non–Q-wave MI with total CK elevation ≥ twice normal in the presence of CK-MB 
elevation and/or troponin elevation). 
EC3. 
Subject has had a cerebrovascular accident or transient ischemic attack clinically confirmed by a 
neurologist or neuroimaging within the past 6 months prior to study enrollment. 
EC4. 
Subject is on renal replacement therapy or has eGFR <20. 
EC5. 
Subject has a pre-existing prosthetic aortic or mitral valve. 
EC6. 
Subject has severe (4+) aortic, tricuspid, or mitral regurgitation. 
EC7. 
Subject has moderate or severe mitral stenosis (mitral valve area ≤1.5 cm2 and diastolic pressure 
half-time ≥150 ms, Stage C or D4). 
EC8. 
Subject has a need for emergency surgery for any reason. 
EC9. 
Subject has a history of endocarditis within 6 months of index procedure or evidence of an active 
systemic infection or sepsis. 
EC10. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or 
paravalvular thrombus requiring intervention. 
EC11. Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count 
<1,000 cells/mm3. 
EC12. Subject has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 
3 months or has other clinically significant bleeding diathesis or coagulopathy that would preclude 
treatment with required antiplatelet regimen or will refuse transfusions. 
EC13. Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated or 
has known hypersensitivity to the protocol required medications (aspirin, all P2Y12 inhibitors, 
heparin), or to the individual components of the test or control valve (nickel, titanium, stainless steel, 
platinum, iridium or polyethylene terephthalate [PET]). 
EC14. Subject has a life expectancy of less than 12 months due to non-cardiac, comorbid conditions based 
on the assessment of the investigator at the time of enrollment. 

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Table 8.3-1: ACURATE IDE Exclusion Criteria 
EC15. Subject has hypertrophic cardiomyopathy. 
EC16. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index 
procedure (except for balloon aortic valvuloplasty, pacemaker implantation, or implantable 
cardioverter defibrillator implantation, which are allowed). 
EC17. Subject has untreated coronary artery disease, which in the opinion of the treating physician is 
clinically significant and requires revascularization. 
EC18. Subject has severe left ventricular dysfunction with ejection fraction <20%. 
EC19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or 
mechanical support devices. 
EC20. Subject has arterial access that is not acceptable for the study device (test or control) delivery 
systems as defined in the device (test or control) Directions For Use. 
EC21. Subject has either of the following: 
• Severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot 
be crossed safely; marked tortuosity; significant narrowing of the abdominal aorta; severe 
unfolding of the thoracic aorta; or thick, protruding, ulcerated atheroma in the aortic arch), OR 
• Severe/eccentric calcification of the aortic annulus that would prevent safe implantation of the 
TAVR prosthesis. 
EC22.  Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the 
subject’s participation in this study. 
EC23. Subject is participating in another investigational drug or device study that has not reached its 
primary endpoint or subject intends to participate in another investigational device clinical trial 
within 12 months after index procedure. 
EC24. Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) 
that in the opinion of the treating physician is clinically significant and requires a pacemaker 
implantation. Enrollment is permissible after permanent pacemaker implantation. 
EC25. Subject has severe incapacitating dementia. 
Abbreviations: CK=creatine kinase; MI=myocardial infarction; TAVR=transcatheter aortic valve 
replacement 
 
Additional exclusion criteria apply to subjects considered for enrollment in the 4D CT 
Imaging Substudy as listed below in Table 8.3-2. 
Table 8.3-2: ACURATE IDE Additional Exclusion Criteria for the 4D CT Imaging 
Substudy 
AEC1.  Subject has eGFR <30 mL/min (chronic kidney disease stage IV or stage V). 
AEC2.  Subject has atrial fibrillation that cannot be rate controlled to ventricular response rate < 60 bpm. 
AEC3.  Subject is expected to undergo chronic anticoagulation therapy after the index procedure. 
 
Note: Subjects treated with short-term anticoagulation post procedure can be included in the 4D CT 
Imaging Substudy; in these subjects the 30-day imaging will be performed 30 days after 
discontinuation of anticoagulation. 
Abbreviations: CT=computed tomography; eGFR=estimated glomerular filtration rate 
 

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9. Subject Accountability 
9.1. 
Point of Enrollment 
9.1.1. 
Roll-In Subjects 
There will be a non-randomized Roll-In phase with only the test device. Centers that do not 
have previous implantation experience with the ACURATE neo™ bioprosthesis 
(transfemoral delivery) will perform at least 2 Roll-In cases before commencing treatment in 
the Main Randomized Cohort; centers with prior experience with ACURATE neo are not 
required to do Roll-In cases. For this Roll-In phase, subjects confirmed eligible for the study 
by the CRC (see Section 21.2) and who provided written informed consent (see Section 20) 
are considered enrolled in the study as soon as an attempt is made to insert the test device 
into the subject’s femoral artery.  
9.1.2. 
Main Randomized Cohort Subjects 
For the Main Randomized Cohort, subjects confirmed eligible for the study by the CRC (see 
Section 21.2) and who provided written informed consent (see Section 20) are considered 
enrolled in the study upon randomization. 
9.1.3. 
ACURATE Prime™ XL Nested Registry Subjects 
For the ACURATE Prime XL Nested Registry, subjects confirmed eligible for the study by 
the CRC (see Section 21.2) and who provided written informed consent (see Section 20) are 
considered enrolled in the study as soon as an attempt is made to insert the test device into 
the subject’s femoral artery. 
9.1.4. 
ACURATE Extended Durability Study Subjects 
Subjects confirmed eligible for the ACURATE Extended Durability Study by the CRC (see 
Section 21.2) and who provided written informed consent (see Section 20) are considered 
enrolled in the study upon randomization. 
9.1.5. 
ACURATE Continued Access Study Subjects 
For the ACURATE Continued Access Study, subjects confirmed eligible for the study by the 
CRC (see Section 21.2) and who provided written informed consent (see Section 20) are 
considered enrolled in the study as soon as an attempt is made to insert the test device into 
the subject’s femoral artery. 
9.2. 
Discontinuation of Study Intervention 
If a test device (ACURATE valve) is explanted during conventional scheduled or emergent 
surgical valve replacement or during an autopsy, if possible, the explanted valve should be 
assessed by the independent histopathology core laboratory for macroscopic and microscopic 

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analyses. Please refer to the study Manual of Operations for recommendations on the explant 
procedure and shipment of the explanted valve.  
If a control device is explanted during conventional scheduled or emergent surgical valve 
replacement or during an autopsy, please follow the directions in the associated DFU/IFU. 
Information on the explant procedure must be documented in source notes and captured in 
the Explant Form of the eCRF. If a study valve is surgically explanted, the subject will be 
followed for safety (no protocol-required echocardiography, electrocardiography or QOL 
assessment) through end of study.  
9.3. 
Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical investigation 
the reason(s) shall be reported. Reasons for withdrawal include but are not limited to 
physician discretion, subject choice to withdraw consent, or death. If such withdrawal is due 
to problems related to investigational device safety or performance, the investigator shall ask 
for the subject’s permission to follow his/her status/condition outside of the clinical study.   
While all efforts will be made to minimize attrition, subjects may withdraw from the study at 
any time, with or without reason, and without prejudice to further treatment. Withdrawn 
subjects will not undergo any additional study follow-up, nor will they be replaced. The 
investigator may discontinue a subject from participation in the study if the investigator feels 
that the subject can no longer fully comply with the requirements of the study or if any of the 
study procedures are deemed potentially harmful to the subject. Data that have already been 
collected on withdrawn subjects will be retained and may be used for analysis, unless local 
regulations apply. No new data will be collected after subject withdrawal.   
All applicable case report forms up to the point of subject withdrawal and an “End of Study” 
form for the subject must be completed. If the withdrawal is due to investigator discretion, 
the investigator should follow-up with the subject per standard of care.  
9.4. 
Lost to Follow-Up 
All subjects implanted will be followed for up to 10 years post-procedure. Enrolled subjects 
who do not have a study device implanted will be assessed through 1-year post procedure for 
safety/adverse events but do not need to have protocol-required echocardiography. A subject 
will be considered “lost to follow-up” and terminated from the study when all criteria listed 
below have been met. 
• Failure to complete 2 consecutive visits without due cause (beginning with the 6-month 
and 1-year visits, i.e., subjects should not be considered lost to follow-up prior to the 
1-year follow-up visit), AND 
• Documentation of 3 unsuccessful attempts, one of which must be in written 
communication, by the Investigator or his/her designee to contact the subject or next of 
kin, AND 

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• Notification from the Investigator to Sponsor reporting subject as lost to follow-up. 
9.5. 
End-of-Study Definition  
This clinical trial will be considered completed when subjects are no longer being examined 
or the last subject’s last study visit as outlined in the data collection schedule (Table 10.1-1) 
has occurred. All subjects who receive a test or control device will be evaluated at discharge 
or 7 days (whichever comes first), 30 days, 6 months, and annually up to 10 years post index 
procedure. Visits at 30 days, 6 months, 1–5 years, 7 years and 10 years are office/clinical/in-
person or telehealth visits. Telephone follow-up is allowed at 6, 8, and 9 years. A subject’s 
participation in the study will be considered complete after the 10-year visit. For subjects 
who do not receive a test or control device, participation in the study will be considered 
complete after the 1-year visit. 
10. Study Methods 
10.1. Data Collection 
This section indicates the data needed to fulfill the objectives of this clinical study. Boston 
Scientific Corporation considers data collected from clinical trial subjects to be personal data 
(see definitions of different data categories in Table 25.2-1) and compliance with privacy 
and data protection laws and regulations (for example, the General Data Protection 
Regulation [GDPR]) to be critically important. Data collection for this clinical study has been 
carefully considered to comply with data privacy laws. 
The data collection schedule is shown in Table 10.1-1 and in Figure 10.1-1. Additional 
information, including recommended post-procedure medical therapy, is provided in 
Section 10.2 through Section 10.11. The methods are based on Valve Academic Research 
Consortium (VARC) metrics66,67 and guideline recommendations4,5. 
All subjects who receive a study valve (test or control) will be evaluated at discharge or 
7 days (whichever comes first), 30 days, 6 months, 1 year, and then annually through 
10 years post index procedure. Office/clinical/in-person or telehealth 
(https/telehealth.hhs.gov) follow-up visits are scheduled for appointed times after the date of 
the index procedure through 5 years and at 7 and 10 years. Telephone follow-up is allowed at 
6, 8, and 9 years. It is important that this schedule be maintained as closely as possible for all 
subjects. Boston Scientific Corporation recognizes that subjects may not be able to return for 
all scheduled visits at precisely the date required and, therefore, a period in which each visit 
is allowed is indicated in Table 10.1-1. Visits/telephone follow-up not completed will be 
considered missed and recorded as protocol deviations and will be reviewed as such by the 
Sponsor or designee on a regular basis in accordance with applicable standard operating 
procedures. Visits/telephone follow-up completed outside these windows will be recorded as 
protocol deviations. Each follow-up must be performed as noted in Table 10.1-1. 
Note: All required ECG measurements and transthoracic echocardiography measurements 
must be done for all subjects who have a transcatheter valve implanted in the aortic position 

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during the index procedure, even if the associated follow-up assessment is carried out via 
telehealth.   
All follow-up dates will be calculated from the date of the (attempted) index procedure (or 
from date of randomization in randomized subjects where no implant is attempted). Subjects 
who are enrolled but do not receive a study valve (test or control) will be followed for 1 year 
to assess for safety but do not need to have protocol required echocardiography, 
electrocardiography, or QOL assessments. If a study valve is surgically explanted, the subject 
will be followed for safety (no protocol required echocardiography, electrocardiography, or 
QOL assessments) through end of study. 

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Table 10.1-1: Data Collection Schedule for ACURATE IDE 
Assessment 
Screeninga 
Baseline 
Procedure 
Within 
1 Day 
Post-
procedure 
Prior to 
Discharge 
or 7 Days 
Post-
Procedure 
30 Daysb 
(±7 Days) 
Office/ 
Telehealth 
Visit 
6 Monthsb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
1 Yearb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
2–5  
Yearsb 
[Annual] 
(±45 Days) 
Office/ 
Telehealth 
Visit 
7 and 10 
Yearsb 
(±60 Days) 
Office/ 
Telehealth 
Visit 
6, 8, and 9 
Yearsb 
(±60 Days) 
Telephone 
Signed Informed Consent 
Formc 
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
Demographics and 
medical history, 
including cardiac, 
neurological, renal and 
peripheral disease  
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
NYHA Classification 
X 
– 
– 
– 
X 
X 
X 
X 
X 
X 
– 
NIHSSd 
– 
X 
– 
– 
X 
– 
– 
X 
– 
– 
– 
Modified Rankin Scaled  
– 
X 
– 
– 
X 
X 
X 
X 
X 
– 
– 
12-lead ECG 
– 
X 
– 
X 
X 
X 
X 
X 
– 
– 
– 
Laboratory testse 
– 
X 
– 
X 
– 
– 
– 
– 
– 
– 
– 
Risk assessmentsf  
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
Frailty, disability and 
comorbidityg 
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
Antiplatelet and 
anticoagulant (if 
applicable) medications 
X 
– 
X 
– 
X 
X 
X 
X 
X 
X 
X 
Other CV medications 
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
TTEh 
X 
– 
– 
– 
X 
X 
X 
X 
X 
X 
– 
TEEi 
– 
– 
O 
– 
– 
– 
– 
– 
– 
– 
– 
Coronary angiogram/CT 
coronary angiogramj 
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
CT angiogram of aortic 
structurek 
X 
– 
– 
– 
– 
 
– 
– 
– 
– 
– 
CT angiogram of 
iliofemoral systeml 
X 
– 
– 
– 
– 
– 
– 
– 
– 
– 
– 
QOL surveysm 
– 
X 
– 
– 
– 
X 
– 
X 
Xn 
– 
– 

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Table 10.1-1: Data Collection Schedule for ACURATE IDE 
Assessment 
Screeninga 
Baseline 
Procedure 
Within 
1 Day 
Post-
procedure 
Prior to 
Discharge 
or 7 Days 
Post-
Procedure 
30 Daysb 
(±7 Days) 
Office/ 
Telehealth 
Visit 
6 Monthsb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
1 Yearb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
2–5  
Yearsb 
[Annual] 
(±45 Days) 
Office/ 
Telehealth 
Visit 
7 and 10 
Yearsb 
(±60 Days) 
Office/ 
Telehealth 
Visit 
6, 8, and 9 
Yearsb 
(±60 Days) 
Telephone 
Procedural cine-
angiography with post-
deployment aortogramo 
– 
– 
X 
– 
– 
– 
– 
– 
– 
– 
– 
Balloon aortic 
valvuloplastyp 
– 
– 
X/O 
– 
– 
– 
– 
– 
– 
– 
– 
AE and ADE 
assessmentsq 
– 
– 
X 
X 
X 
X 
X 
X 
– 
– 
– 
Device deficiencies, 
SAE, SADE, UADE and 
CEC event assessmentsr 
– 
– 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4D CT imaging of 
prosthetic valves 
– 
– 
– 
– 
– 
X 
– 
X 
– 
– 
– 
Note: X = required; O = optional; – = not required; follow-up should be done by study personnel or as noted below. Visits at 30 days, 6 months, 1–5 years, 7 years and 10 years are 
office/clinical/in-person or telehealth visits; all required ECG measurements and TTE measurements must be done for all subjects who have a transcatheter valve implanted in the aortic 
position during the index procedure, even if the associated follow-up assessment is carried out via telehealth. 
a:  Screening materials for CRC review should be submitted electronically at least 5 days in advance of CRC review. 
b: All follow-up dates will be calculated from the date of the (attempted) index procedure (or from date of randomization for randomized subjects where no implant is attempted). Where 
indicated, visits must be an office/clinical/in-person visit but may be done in-hospital should the subject be admitted at the time. Subjects who are enrolled but do not receive a study 
device (test or control) will be followed for 1 year to assess for safety but do not need to have protocol required TTE, ECG or QOL assessments. 
c:  Study-specific consent includes screening consent to perform required assessments beyond standard of care that will be evaluated by the CRC to confirm subject eligibility. If the 
study Informed Consent Form is modified during the course of the study, study subjects will be re-consented as necessary.  
d:   NIHSS and mRS must be performed by a neurology professional or certified personnel (external certification for NIHSS; internal or external certification for mRS). The NIHSS and 
mRS assessors should be independent (not involved with the care of study subjects). In addition to the assessments noted in the table, there are additional requirements for 
administering NIHSS/mRS/neurological physical exams in subjects where stroke is suspected. A neurological physical exam conducted by an independent neurologist, neurology 
fellow, neurology physician assistant, or neurology nurse practitioner must be performed in all subjects where stroke is suspected. For subjects diagnosed with a neurological event, 
mRS and NIHSS must be performed after the event; mRS must also be administered at 90±14 days after a stroke. If a subject who has not received a study device (investigational or 
control) experiences a neurological event within the first 1 year after the index procedure, mRS must be performed on that subject after the event; mRS must also be administered at 
90±14 days after a stroke and the results must be reported to the Sponsor.    
e:   Laboratory tests at baseline include CBC with platelets, albumin, serum creatinine, and cardiac enzymes. Cardiac enzymes (CK is required, CK-MB or troponin if CK is elevated) 
must be collected twice at intervals per standard of care within 6–24 hours post-procedure. Acute kidney injury should be assessed through discharge/7 days based on the AKIN 
system. 
f:  Consists of STS PROM score, euroSCORE II, and heart team assessment including an in-person evaluation by a center cardiac surgeon that must be confirmed by the CRC (which 
must include an experienced cardiac surgeon).  

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Table 10.1-1: Data Collection Schedule for ACURATE IDE 
Assessment 
Screeninga 
Baseline 
Procedure 
Within 
1 Day 
Post-
procedure 
Prior to 
Discharge 
or 7 Days 
Post-
Procedure 
30 Daysb 
(±7 Days) 
Office/ 
Telehealth 
Visit 
6 Monthsb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
1 Yearb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
2–5  
Yearsb 
[Annual] 
(±45 Days) 
Office/ 
Telehealth 
Visit 
7 and 10 
Yearsb 
(±60 Days) 
Office/ 
Telehealth 
Visit 
6, 8, and 9 
Yearsb 
(±60 Days) 
Telephone 
g:   Frailty, disability, and comorbidity risk assessments must be captured at screening: height, weight, strength and balance (use of wheelchair, gait speed to walk 5 meters, number of 
falls in the past 6 months, maximal grip strength), and activities of daily living (Katz Index).   
h:  Transthoracic echocardiogram is required for all subjects who have a study valve implanted in the aortic position. This includes assessment of EOA, peak and mean aortic valve 
pressure gradients, peak aortic velocity, aortic regurgitation assessment, and LVEF. Screening TTE must be performed within 90 days prior to CRC approval. At least 1 
echocardiogram must be obtained before discharge or 7 days (whichever comes first); if multiple echocardiographic studies are performed prior to discharge and within 7 days of the 
procedure, the latest study performed will be used for analysis. All TTEs must be performed according to the Echocardiography Core Laboratory procedure guidelines (see study 
Manual of Operations). If a subject does not receive a study valve, then no follow-up TTE is required.  
Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction <50%), dobutamine can be used to assess the grade of aortic stenosis; the 
subject may be enrolled if echocardiographic criteria are met with this augmentation. In cases where a subject who has met the echocardiographic criteria for enrollment receives BAV 
prior to the index procedure and subsequently no longer meets the study’s aortic valve pressure gradient or EOA criteria, the subject may still be enrolled based on the pre-BAV 
echocardiographic data. In such cases, the most recent echocardiogram done prior to the index procedure (even if after BAV) must be submitted to the echocardiography core 
laboratory to be included in the baseline data.  
i: TEE can be performed at the discretion of the operator. 
j:  A coronary angiogram/CT coronary angiogram must be performed within 365 days prior to CRC approval. If there is concern regarding the current extent of coronary artery disease 
or aortic stenosis, the CRC may recommend a repeat study closer to the time of enrollment.     
k:  A CT angiogram of the aortic complex must be performed within 180 days prior to CRC approval (and should be performed within 90 days if possible) to evaluate the aortic valve 
anatomy and aortic root dimensions for device sizing. CT angiogram must be performed according to the CT/Angiography Core Laboratory procedure guidelines (see study Manual of 
Operations). It must be sent to the core laboratory for detailed measurements and analyses in advance of the CRC review where results will be assessed to confirm subject’s eligibility. 
l:   An assessment of the iliofemoral system must be performed within 180 days prior to CRC approval (and should be performed within 90 days if possible).  A CT angiogram of the 
iliofemoral system should be performed for complete visualization of the iliac and femoral arteries to assess for dimensions, tortuosity, and calcification. The CT angiogram should be 
performed per the procedure guidelines (see study Manual of Operations) and sent to the CT core laboratory with the screening CT angiogram of the aortic structure. An iliofemoral 
invasive angiogram may be substituted for the iliofemoral CT angiogram. 
m: Includes the Kansas City Cardiomyopathy and SF-12 QOL questionnaires. Baseline QOLs must be performed within 30 days prior to the index procedure. 
n:  QOL survey at 5 years. 
o: Procedural cine-angiogram including the baseline images of the aortic complex and the final post-deployment aortogram of the ascending aorta must be performed and sent to the 
CT/Angiography core laboratory for analysis.  
p: Balloon aortic valvuloplasty following standard techniques must be performed with an appropriately sized valvuloplasty balloon before test device implantation; BAV may be 
performed before control device implantation, but planned use should be reviewed by the CRC. 
q: In subjects who receive a study device, AEs and ADEs will be monitored and collected from the time of enrollment through 12-month follow-up. For subjects who do not receive a 
study device, AEs will be monitored through 12-month follow-up.  
r:  Information on device deficiencies for the test device will be monitored and reported to Boston Scientific. Information on all SAEs, SADEs, UADEs, and CEC events will be 
monitored and reported to Boston Scientific for enrolled subjects from the time of enrollment through 5 years. After 5 years, serious adverse event assessment (includes SAE, SADE, 
UADE, and relevant VARC events to be adjudicated by the CEC [see Note below]) for test and control device(s) and device deficiencies assessment for test device(s) with associated 
treatment will be monitored and reported to Boston Scientific for enrolled subjects through termination of the study (or until a subject exits the study). For subjects who are enrolled 

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Table 10.1-1: Data Collection Schedule for ACURATE IDE 
Assessment 
Screeninga 
Baseline 
Procedure 
Within 
1 Day 
Post-
procedure 
Prior to 
Discharge 
or 7 Days 
Post-
Procedure 
30 Daysb 
(±7 Days) 
Office/ 
Telehealth 
Visit 
6 Monthsb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
1 Yearb 
(±30 Days) 
Office/ 
Telehealth 
Visit 
2–5  
Yearsb 
[Annual] 
(±45 Days) 
Office/ 
Telehealth 
Visit 
7 and 10 
Yearsb 
(±60 Days) 
Office/ 
Telehealth 
Visit 
6, 8, and 9 
Yearsb 
(±60 Days) 
Telephone 
with an attempted procedure but no implanted study valve (test or control), the aforementioned events will be monitored through 1-year post-index procedure. For randomized 
subjects with no index procedure, the aforementioned events will be monitored through 1-year post randomization. Please refer to Section 19.1 for a list of CEC events and Table 
25.2-1 for definitions of these events, which specify data required for CEC adjudication. Complaint reporting of any device deficiencies for any commercially available products used 
should be carried out using the manufacturer’s processes. 
Note: Relevant VARC events after 5 years to be adjudicated by the CEC include the following: mortality, stroke, spontaneous myocardial infarction, acute kidney injury, repeat 
procedure for valve-related dysfunction, hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA III or IV), new pacemaker, new onset atrial 
fibrillation or atrial flutter, prosthetic aortic valve malpositioning (valve migration, valve embolization, or ectopic valve deployment), TAV-in-TAV, prosthetic aortic valve 
thrombosis and endocarditis.  
s: This applies to subjects in the 4D CT Imaging Substudy. Please refer to the CT Core Laboratory procedure guidelines (see study Manual of Operations). Results must be sent to the 
CT Core Laboratory (see Section 13.3.2). 
Note: For subjects in the CT Imaging Substudy, the visits at 30 days and 1 year must be done in the clinic (or in-hospital). 
Abbreviations: AE=adverse event; ADE=adverse device effect; AKIN=Acute Kidney Injury Network; BAV=balloon aortic valvuloplasty; CBC=complete blood count; CEC=Clinical 
Events Committee; CK-MB=creatine kinase-myoglobin band; CRC=Case Review Committee; CT=computed tomography; CV=cardiovascular; ECG=electrocardiogram; EOA=effective 
orifice area; mRS=modified Rankin Scale; NIHSS=National Institutes of Health Stroke Scale; NYHA=New York Heart Association; QOL=Quality of Life; SAE=serious adverse event; 
SADE=serious adverse device effect; STS=Society of Thoracic Surgery; TEE=transesophageal Doppler echocardiography; TTE=transthoracic Doppler echocardiography; 
UADE=unanticipated adverse device effect 

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Figure 10.1-1: Data Collection Schedule for ACURATE IDE 
See Table 10.1-1 for additional information. 

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10.2. Study Candidate Screening 
Subjects will be evaluated for eligibility by the center heart team (which must include an 
experienced cardiac interventionalist and an experienced cardiac surgeon). The heart team 
should consider the Society of Thoracic Surgeons (STS) score as well as other factors 
including frailty, prior surgical history, malignancy or radiation therapy, pulmonary disease, 
renal disease, liver disease, neuromuscular disease, orthopedic disease, chest deformity, and 
aortic calcification. Eligible subjects will have agreement from the heart team that the subject 
is indicated for TAVR (see Table 8.2-1 for inclusion criteria; see definition of operative risk 
in Table 25.2-1). Risk of operative mortality and morbidity is to be assessed via an in-person 
evaluation by a center cardiac surgeon and must be confirmed by the CRC (which must 
include an experienced cardiac surgeon). The heart team must also agree that the subject is 
likely to benefit from valve replacement.   
Screening assessments are detailed in Section 10.4 below. Clinical assessment and 
evaluation, collected tests and images (e.g., echocardiography, computerized tomography 
[CT], angiography) performed in preparation for TAVR, and planned use of balloon aortic 
valvuloplasty (BAV) will be reviewed by the CRC (see Section 7.2 and Section 21.2). 
Informed consent will be obtained before any study-specific screening procedures in advance 
of TAVR that go beyond standard of care. The CRC will be comprised of experienced 
cardiac surgeons, experienced interventional cardiologists, and Sponsor staff proficient with 
the ACURATE Transfemoral Aortic Valve System and will confirm subject eligibility for 
enrollment. 
10.2.1. Strategies for Recruitment and Retention 
The ACURATE IDE study will include subjects presenting with documented severe native 
aortic valve stenosis who are indicated for TAVR (Section 8.2). It is estimated that nearly 5% 
of elderly ≥75 years of age have aortic stenosis and its prevalence is expected to increase due 
to an aging population2,3. Because aortic stenosis most commonly occurs in the very elderly, 
women are well represented in TAVR trials. Traditionally underrepresented populations are 
expected to be included in the subject population as allowed by governing law/national 
regulation; as the very elderly will represent the majority of subjects enrolled in the trial, 
efforts to maximize retention are by definition targeted to traditionally under-represented 
groups. The inclusion and exclusion criteria are not expected to have a negative effect on 
recruitment or retention of said populations. In the United States, the subjects eligible for 
inclusion in this study are likely to be Medicare patients due to their expected age and the 
results of this study are likely to be highly generalizable to a Medicare population.  
All efforts will be made to minimize attrition (see Section 9.4). Investigators are encouraged 
to enroll subjects who are willing to comply with the follow-up requirements of the study. If 
a visit is missed, the center should attempt to contact the subject to reschedule the missed 
visit and counsel the subject on the importance of maintaining the assigned visit schedule.  

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10.3. Subject Informed Consent 
Informed consent (see Section 20) must be obtained from a potential subject prior to 
conducting any preoperative assessments that are not part of the local routine preparation and 
evaluation of a subject for TAVR, even if the subject’s eligibility has not yet been completely 
determined.   
The Investigator/designee, who has been trained on the protocol, will explain the nature and 
scope of the study, potential risks and benefits of participation, and answer questions for the 
subject. If the subject agrees to participate, the Institutional Review Board (IRB)/Research 
Ethics Board (REB)/Human Research Ethics Committee (HREC)/Independent Ethics 
Committee (IEC)-approved Informed Consent Form (ICF) must be signed and personally 
dated by the subject or his/her legally authorized representative at the time of consent. The 
Investigator/designee must also sign and date the ICF at the time of consent and prior to 
subject enrollment. Any additional persons required by the center’s IRB/REB/HREC/IEC to 
sign the ICF must also comply. Study personnel should explain to the subject that even if the 
subject agrees to participate in the study and signs the ICF, the heart team and/or the CRC 
may determine that the subject is not a suitable candidate for the study and/or TAVR 
procedure. 
If during preoperative evaluations, the subject is found not to be eligible for inclusion in the 
study, the subject should be notified. Reason for ineligibility will be accounted for as 
“screening failure” and will be documented as such in the eCRF screening module. If the 
subject has signed the ICF but is found not eligible for inclusion in the study prior to or 
during the procedure, the subject should receive the appropriate treatment as identified by the 
clinical investigator. Information regarding the screening failure will be captured on the 
screening module and the subject will be included in the “screening cohort” accountability.  
Note: Centers may use remote consent as allowed by institutional policy and the center’s 
IRB/REB/HREC/IEC. 
10.4. Screening Assessments 
Results from the screening tests and procedures listed below (including planned control 
device if subject is randomized to the control arm and planned use of BAV with the control 
device during the index procedure) must be submitted to the CRC (see Section 21.2) for 
evaluation to confirm a subject’s eligibility for the study. Screening assessment 
documentation should be provided via electronic upload at least 5 days in advance of a 
scheduled CRC review or at least 5 days in advance of the planned procedure date. It is 
expected that CRC reviews will take place at least weekly or as needed to ensure timely 
review and confirmation of subject eligibility. For the randomized cohort, a subject should be 
randomized after CRC approval and within 7 calendar days of CRC approval. 
Centers will be trained on the screening process as detailed in the ACURATE IDE Training 
Plan (see Section 16.4.2). Specific data points will be collected in the ACURATE IDE 
electronic Case Report Forms (eCRFs) as shown below.  

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• Clinical assessments  
o Demographics including age and gender 
o Medical history (general medical; cardiac [including previous cardiac surgery]; 
neurological, renal [including creatinine] and peripheral disease; and other medical 
conditions)   
o Physical examination including weight and height 
o NYHA classification 
o Current antiplatelet and other cardiovascular medications 
o Planned use of BAV (i.e., predilation) 
o Risk assessments: Society of Thoracic Surgeons (STS) score, euroSCORE II, heart 
team assessment including an in-person evaluation by a center cardiac surgeon and 
any frailty assessments (detailed in next bullet). In the United States, CMS currently 
requires independent evaluation by 1 cardiac surgeon for reimbursement. 
• Frailty, disability, and comorbidity assessments (collected prospectively)74,75  
o Body Mass Index from the physical exam 
o Strength and balance  
- Use of wheelchair 
- Gait speed as measured by a stopwatch for a subject to walk 5 meters 
(3 measures averaged)75-77  
- Number of falls in the past 6 months 
- Maximal grip strength (kg) in the dominant hand (3 measures averaged), using a 
hand-held dynamometer78  
o Activities of daily living: Katz Index74,79 is based on an evaluation of the functional 
independence or dependence of a subject in bathing, dressing, going to toilet, 
transferring, continence, and feeding. A point is assigned for independence in each 
of the 6 functions, and 0 points if there is any dependence in these 6 categories. 
• Imaging assessments  
o Within 90 days prior to CRC approval, TTE (2-D, M-Mode, and color) must be 
carried out. The evaluation should include assessment of effective orifice area 
(EOA), peak and mean aortic valve gradient pressure, aortic regurgitation 
assessment, mitral regurgitation, left ventricular ejection fraction (LVEF), left 
ventricular end-diastolic and end-systolic diameter, tricuspid regurgitation (TR) jet 
velocity, and left atrial (LA) volume. The TTE must be performed according to the 
Echocardiography Core Laboratory procedure guidelines (see study Manual of 
Operations). For enrolled subjects, the TTE must be provided to the 
echocardiography core laboratory for independent analyses. In cases of low 
flow/low gradient aortic stenosis with left ventricular dysfunction (ejection fraction 
<50%), dobutamine can be used to assess the grade of aortic stenosis (maximum 
dobutamine dose of 20 mcg/kg/min recommended)4; the subject may be enrolled if 
echocardiographic criteria are met with this augmentation. In cases where a subject 

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who has met the echocardiographic criteria for enrollment receives BAV prior to 
the index procedure and subsequently no longer meets the ACURATE IDE aortic 
valve pressure gradient or EOA criteria, the subject may still be enrolled based on 
the pre-BAV echocardiographic data. In such cases, the most recent 
echocardiogram done prior to the index procedure (even if after BAV) must be 
submitted to the echocardiography core laboratory to be included in the baseline 
data.     
o A coronary angiogram/CT coronary angiogram must be performed within 365 days 
prior to CRC approval. If there is concern regarding the current extent of coronary 
artery disease or aortic stenosis, the CRC may recommend a repeat study closer to 
the time of enrollment. An aortogram and hemodynamics including simultaneous 
ascending aorta and left ventricle pressure measurements should be performed.  
o A CT angiogram of the aortic complex must be performed 180 days prior to CRC 
approval (and should be performed within 90 days if possible) to evaluate the aortic 
valve anatomy and aortic root dimensions to determine eligibility and device sizing. 
It must meet the CT/Angiography Core Laboratory procedure guidelines (see study 
Manual of Operations) and be provided in advance to the core laboratory for 
detailed measurements and independent analyses, which will be reviewed by the 
CRC to confirm a subject’s eligibility. 
o An assessment of the iliofemoral system must be performed within 180 days prior 
to CRC approval (and should be performed within 90 days if possible). A CT 
angiogram of the iliofemoral system should be performed for complete 
visualization of the iliac and femoral arteries to assess for dimensions, tortuosity, 
and calcification. The CT angiogram of the iliofemoral system should be performed 
per the procedure guidelines (see study Manual of Operations) and provided to the 
CT/Angiography Core Laboratory with the screening CT angiogram of the aortic 
structure for independent measurements and review by the CRC to confirm a 
subject’s eligibility. An iliofemoral invasive angiogram may be substituted for the 
iliofemoral CT angiogram. 
10.5. Baseline Assessments 
The following assessments must be completed within 30 days prior to the index procedure, 
unless otherwise specified below. The ACURATE IDE electronic CRFs identify the specific 
data points to be collected. 
• Confirmation of CRC approval date 
• NIH Stroke Scale (NIHSS), which must be performed by a neurology professional or 
certified personnel (external certification); NIHSS assessors should be independent (not 
involved with the care of study subjects) 
• Modified Rankin Scale (mRS) score, which must be performed by a neurology 
professional or certified personnel (external or internal certification); mRS assessors 
should be independent (not involved with the care of study subjects) 

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• 12-lead electrocardiogram (ECG) 
• Laboratory tests 
o Complete blood count (CBC) with platelets 
o Albumin 
o Serum creatinine 
o Cardiac enzymes (creatine kinase [CK] is required, CKMB or troponin if CK is 
elevated) 
• Quality Of Life (QOL) Surveys: Kansas City Cardiomyopathy71 and SF-1272 QOL 
Questionnaires  
Note: In cases where a subject who has met the echocardiographic criteria for enrollment 
receives BAV prior to the index procedure and subsequently no longer meets the ACURATE 
IDE aortic valve pressure gradient or EOA criteria, the subject may still be enrolled based on 
the pre-BAV echocardiographic data. In such cases, the most recent echocardiogram done 
prior to the index procedure (even if after BAV) must be submitted to the echocardiography 
core laboratory to be included in the baseline data. 
10.6. Pre-procedure Medications 
Pre-procedure medications are listed below. 
• Antiplatelet therapy (aspirin plus a P2Y12 inhibitor) is recommended prior to valve 
implantation.  
o Aspirin: A loading dose of aspirin (recommended dose of 75–325 mg) is 
recommended for subjects who have not been on aspirin therapy for ≥72 hours at 
the time of the index procedure. The loading dose should be administered prior to 
the implant procedure. Subjects who have been taking aspirin daily for ≥72 hours at 
the time of the index procedure do not require a loading dose. 
o P2Y12 Inhibitor: A loading dose of a P2Y12 inhibitor (recommended dose of 
≥300 mg for clopidogrel, 60 mg for prasugrel, 180 mg for ticagrelor) is 
recommended for subjects who have not been on P2Y12 therapy for ≥72 hours at the 
time of the index procedure. The loading dose should be administered prior to the 
implant procedure. 
Note: If a subject is treated with anticoagulation, either a P2Y12 inhibitor or aspirin 
is recommended prior to the implant procedure, but not both. 
• Anticoagulant therapy (e.g., unfractionated heparin) must be administered per local 
standard of care during the implant procedure, with a recommended target activated 
clotting time (ACT) of ≥250 seconds during the implantation procedure. 
• Prophylactic antibiotic therapy should be given according to local practice. The choice 
of antibiotic drug is left to the investigator’s discretion. 

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10.7. Index Procedure 
The TAVR procedures will be performed at centers and by operators trained in implanting 
both the control and test devices. The preparation of both valves will be conducted by 
experienced and certified personnel. In the United States, CMS coverage criteria currently 
require that cardiac surgeon and interventional cardiologist members of the heart team 
participate in the technical aspects of the index procedure. 
The preparation of the subject for the procedure will be performed following standard 
techniques. Balloon aortic valvuloplasty following standard techniques must be performed 
with an appropriately sized valvuloplasty balloon before test device implantation; BAV is 
optional for the control device and at the discretion of the physician.  
Transfemoral access must be attempted for all subjects (assessment of the iliofemoral system 
prior to subject enrollment must indicate that transfemoral access is considered appropriate). 
If the transfemoral approach is unsuccessful, the operator will decide the best alternative 
approach to treat the subject.   
10.7.1. Control Cohort 
The DFU/IFU associated with the control device should be followed. A balloon 
valvuloplasty on the existing valve following standard techniques may be performed with an 
appropriately sized valvuloplasty balloon before control device implantation. A final post-
deployment aortogram of the ascending aorta must be performed and forwarded to the 
computed tomography/angiography core laboratory with the procedural cine-angiogram for 
analysis. 
Labels from devices used during the procedure (e.g., transcatheter heart valve, introducer, 
etc.) should be retained so that they can be included in the appropriate source documents and 
reported in the eCRFs. During the procedure, designated center study personnel must capture 
necessary information on acute device/delivery system performance and procedure. The 
following information will be collected during the procedure. 
• Date of procedure 
• Success of each attempted valve implant 
• Specifics of device(s) used (such as size and model) 
• Time of puncture (at site of TAVR sheath) and time of vascular closure for TAVR 
sheath (introducer insertion and removal time) 
• Descriptive information on balloon valvuloplasty, if performed (e.g., size of balloon, 
number of balloon inflations) 
• Any devices used and adjunctive procedures performed during the implant procedure  
• Valve catheter insertion and removal time 
• Descriptive information on valve implantation procedure  

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• Adverse event (AE) assessment and associated treatment (including AE, serious 
adverse event [SAE], serious adverse device effect [SADE], unanticipated adverse 
device effect [UADE], adverse device effect [ADE] and Clinical Events Committee 
[CEC] events; see Section 19.1) 
Note: For subjects randomized to the Control group who do not receive the intended 
Control valve, the valve type actually implanted must be recorded.   
10.7.2. ACURATE Transfemoral Aortic Valve System (Test) Cohort 
The DFUs/IFUs for the ACURATE Transfemoral Aortic Valve System should be followed. 
The commercially available 14F iSLEEVE introducer sheath (see Section 5.1.3) shall be 
prepared and placed in the subject’s femoral artery as per the introducer DFU/IFU. . 
10.7.2.1. Valvuloplasty 
Following standard techniques and using an appropriately sized valvuloplasty balloon, BAV 
must be performed on the existing valve before implantation of the ACURATE valve. 
Careful attention should be paid to the position of the guidewire throughout the BAV 
procedure. Prior to introduction of the ACURATE Transfemoral Aortic Valve System, the 
subject’s hemodynamic status must be assessed (12-lead ECG is not required).  
Information on the BAV, including number of inflations, should be documented in the source 
data and will be captured in the eCRFs. 
10.7.2.2. Preparing and Using the ACURATE Transfemoral Aortic Valve System 
All operators must comply with the appropriate DFU/IFU and must be adequately trained 
and certified by BSC personnel in accordance with the training plan before performing the 
procedure (see Section 16.4.2 for additional information on training). Guidelines provided by 
the Sponsor for valve size selection should be followed.  
The ACURATE Transfemoral Aortic Valve System (valve plus transfemoral delivery 
system) must be prepared in accordance with the appropriate DFU/IFU and other training 
material (see Section 16.4.2). Device preparation should only be performed by certified 
persons who have completed applicable training with the ACURATE Transfemoral Aortic 
Valve System (Section 16.4.2).   
Prior to insertion of the ACURATE Transfemoral Aortic Valve System catheter into the 
introducer, the recommended target ACT (≥250 seconds) should be confirmed, with 
additional boluses of heparin administered if needed.  
The appropriate DFU/IFU should be followed. The procedure is briefly summarized below 
for the ACURATE neo2™ Transfemoral Aortic Valve System. A similar procedure is used 
for preparation of the ACURATE Prime Aortic Valve XL; please see the corresponding 
DFU/IFU and other training material provided by BSC. All steps described below shall be 
performed under fluoroscopic control and with optional transesophageal echocardiography 
guidance. 

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1) The ACURATE neo2 valve is loaded onto the ACURATE neo2 delivery catheter 
following the DFU/IFU. A compatible introducer sheath is placed in the femoral artery 
and the ACURATE neo2 delivery catheter with the ACURATE neo2 valve is introduced 
transfemorally over a 0.035 in (0.89 mm) guidewire, maintaining proper guidewire 
positioning across the existing valve and into the ventricle.  
2) The delivery system with valve is carefully advanced through the aorta and the aortic 
arch and is preliminarily positioned with the distal tip across the calcified native aortic 
valve through the ascending aorta (see Figure 10.7-1, Position 1).  
3) The first rotating knob is turned counterclockwise, retracting the outer member of the 
delivery system containing the ACURATE neo2 valve; the upper crown and 
stabilization arches are deployed and contact the ascending aorta (Figure 10.7-1, 
Position 2). This orients the system towards the longitudinal direction of the aorta 
(Figure 10.7-1, Position 3). The upper crown should be positioned slightly above the 
aortic annular plane. An optional episode of rapid ventricular pacing may facilitate the 
final confirmation of the optimal positioning. 
4) The second rotating knob is turned, which advances the capsule, and the 
ACURATE neo2 valve detaches from the delivery system leaving the lower crown fully 
expanded. The diabolo shape of the two anchoring crowns facilitates conformation to the 
calcified annulus and results in stable positioning (Figure 10.7-1, Position 4). 
5) The tip and capsule of the delivery system are carefully retracted through the functioning 
valve. 
6) After withdrawing through the valve, the delivery system is retracted into the descending 
aorta and the capsule over the stent holder is closed by turning the second rotating knob. 
The system is pulled out of the body. 
7) A final post-deployment aortogram of the ascending aorta must be performed and 
forwarded to the core laboratory with the procedural cine-angiogram for analysis. 
8) The introducer is then removed.  
9) The femoral access is closed according to standard practice. 
 

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Figure 10.7-1: Valve Implantation Procedure 
Position 1: Delivery system is placed through the native valve. Position 2: The upper anchoring crown is 
deployed. Position 3: The stabilization arches are deployed, and partial release is achieved. Position 4: The 
lower anchoring crown is deployed, and final release is achieved. 
Note: This example shows the ACURATE neo2 valve. 
Labels from the devices used during the procedure (e.g., valve, introducer, etc.) should be 
retained so that they can be included in the appropriate source documents and reported in the 
eCRFs.   
During the procedure, designated center study personnel must capture necessary information 
on acute device/delivery system performance and procedure. The following information will 
be collected during the procedure. 

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• Date of procedure 
• Device size (Small, Medium, Large, or Extra Large)  
• Time of puncture (at site of TAVR sheath) and time of vascular closure for TAVR 
sheath (introducer insertion and removal time) 
• Descriptive information on balloon valvuloplasty (e.g., size of balloon, number of 
balloon inflations) 
• Any devices used and adjunctive procedures performed during the implant procedure  
• ACURATE Transfemoral Aortic Valve System catheter insertion and removal time 
• Descriptive information on the valve implantation procedure 
• Adverse event assessment and associated treatment (including AE, SAE, SADE, 
UADE, ADE, and CEC events; see Section 19) 
• Device deficiencies assessment for the ACURATE Transfemoral Aortic Valve System  
Note: All ACURATE transfemoral aortic valve implantation procedures will be performed 
with the support/presence of trained BSC personnel.    
10.8. Post Index Procedure 
The following are to be performed post-procedure. 
• Per society guidelines4,5 antiplatelet therapy is recommended to reduce the risk of 
thrombotic or thromboembolic complications if there are no contraindications to these 
medications. Subjects must be treated with antiplatelet therapy (aspirin and/or a P2Y12 
inhibitor) for at least 1 month following valve implantation. Extended dual antiplatelet 
therapy may be administered per physician choice. It should be noted, however, that 
recent clinical evidence points to increased bleeding risk post TAVR among subjects 
receiving dual antiplatelet therapy or antiplatelet therapy plus anti-coagulation (among 
subjects indicated for anti-coagulation)80,81. 
 
o After the valve implant procedure, aspirin (recommended dose of ≥75 mg daily) 
and/or a P2Y12 inhibitor must be given for at least 1 month. It is recommended that 
daily aspirin be given indefinitely thereafter as per local standard of care. Aspirin 
dose may be adjusted to the closest approximation based on local tablet formulation 
availability. The P2Y12 inhibitor choice and dosing should be per local standard of 
care. 
o If a subject is treated with anticoagulation, either a P2Y12 inhibitor or aspirin is 
recommended after the implant procedure in addition to the anticoagulant therapy 
(but treatment with both aspirin and a P2Y12 inhibitor after the implant procedure is 
not recommended). The subject should be treated with an oral anticoagulant (OAC) 
and either a P2Y12 inhibitor or aspirin for at least 1 month. After 1 month, subjects 
requiring chronic anticoagulation may be treated at the discretion of the treating 
physician. 

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• Prophylactic antibiotic regimen should be completed per local practice. 
• Additional medications may be used at the investigator’s discretion. 
• It is recommended that the subject’s heart rhythm be monitored using telemetry for at 
least 48 hours after the index procedure.    
• 12-lead ECG must be completed within 24 hours post-procedure.   
• Cardiac enzymes (CK is required, CK-MB or troponin if CK is elevated) must be 
collected twice at intervals per standard of care within 6–24 hours post-procedure. 
10.9. Prior to Discharge or 7 Days Post-Procedure (Whichever Comes First) 
Subjects must be evaluated prior to discharge or 7 days post-procedure (whichever comes 
first) based on the assessments below. The ACURATE IDE eCRFs identify the specific data 
points to be collected. 
• Weight  
• NYHA classification 
• NIHSS, which must be performed by a neurology professional or certified personnel 
(external certification); NIHSS assessors should be independent (not involved with the 
care of study subjects).  
• Modified Rankin Scale score, which must be performed by a neurology professional or 
certified personnel (external or internal certification); mRS assessors should be 
independent (not involved with the care of study subjects). 
• 12-lead ECG     
• TTE, including assessment of EOA, peak and mean aortic valve gradient pressure, 
aortic regurgitation assessment, mitral regurgitation, LVEF, left ventricular end-
diastolic and end-systolic diameter, TR jet velocity and LA volume, per the 
Echocardiography Core Laboratory procedure guidelines (see study Manual of 
Operations).  All TTEs for enrolled subjects must be provided to the echocardiography 
core laboratory for independent analyses.  
 
Note: For all subjects who have a valve implanted in the aortic position during the 
index procedure at least 1 echocardiogram must be obtained before discharge or 7 days 
(whichever comes first); if multiple echocardiographic studies are performed prior to 
discharge and within 7 days of the procedure, the latest study performed will be used 
for analysis. Subjects who do not receive a study valve during the index procedure are 
not required to have follow-up TTE.   
• Current antiplatelet and anticoagulant (if applicable) medications 
• Complete adverse event (AE, SAE, SADE, UADE, ADE, and CEC events) assessment 
for test and control devices and device deficiencies assessment for the test device, with 
associated treatment. 

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10.10. Follow-up 
All subjects implanted with a study valve (test or control) will be evaluated per the schedule 
in Table 10.1-1. Subjects who are enrolled and have an attempted procedure but do not 
receive a study valve (test or control) will be assessed through 1-year post index procedure 
for safety/adverse events but do not need to have protocol required echocardiography. 
Randomized subjects who do not have an attempted index procedure will be assessed 
through 1-year post randomization but do not need to have protocol required 
echocardiography. Subjects who receive a surgical valve will be followed through the end of 
the study but do not need to have protocol required echocardiography. Data from the required 
tests and images as well as medical assessments will be recorded in source documentation 
and captured in the eCRFs. The determination of specified study endpoints and 
measurements such as valve function and CEC events will require data from images and tests 
as outlined in the event definitions (Table 25.2-1).    
If study personnel learn of a subject’s hospitalization outside the study center, the center 
should make every effort to obtain copies of reports or results based on tests (e.g., 
echocardiogram) and/or procedures performed on the study subject.  
Note 1: A subject who has received a study valve should not be enrolled in a clinical trial of 
an investigational drug/device/treatment until the subject has reached the ACURATE IDE 
primary endpoint (1 year). 
Note 2: Where indicated in Table 10.1-1, the follow-up visits must be conducted in-person 
or as telehealth visits. If an in-person/telehealth assessment cannot be performed, follow-up 
by telephone call should be attempted. The subject or the subject’s physician should provide 
rationale for why the subject cannot comply with the follow-up in-person/telehealth 
assessment.  
10.10.1. 30-Day Follow-up (30±7 Days)  
All enrolled subjects must be evaluated 30 (±7) days after the index procedure in person or 
via telehealth. During the 30-day follow-up visit, the following assessments must be 
completed. The ACURATE IDE eCRFs identify the specific data points to be collected. 
• Weight  
• NYHA classification  
• Modified Rankin Scale score, which must be performed by a neurology professional or 
certified personnel (external or internal certification); mRS assessors should be 
independent (not involved with the care of study subjects). 
• 12-lead ECG 
Note 1:  A 12-lead ECG must be obtained for all subjects, even if the associated follow-
up assessment is carried out via telehealth.     
• Current antiplatelet, anticoagulant (if applicable) medications 

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• TTE including assessment of EOA, peak and mean aortic valve gradient pressure, 
aortic regurgitation assessment, mitral regurgitation, LVEF, left ventricular end-
diastolic and end-systolic diameter, TR jet velocity and LA volume.  TTE must be 
performed per the Echocardiography Core Laboratory procedure guidelines (see study 
Manual of Operations). All TTEs for enrolled subjects must be provided to the 
echocardiography core laboratory for independent analyses. 
 
Note 2: TTE must be done for all subjects who have a transcatheter valve implanted in 
the aortic position during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth. Enrolled subjects who have an attempted 
procedure but do not receive a transcatheter valve are not required to have follow-up 
TTE.  
• Quality of Life Surveys: Kansas City Cardiomyopathy and SF-12 Quality of Life 
Questionnaires 
• Complete adverse event (AE, SAE, SADE, UADE, ADE and CEC events) assessment 
for test and control devices and device deficiencies assessment for test device(s), with 
associated treatment 
• For subjects enrolled in the CT Imaging Substudy, assessment of prosthetic valve 
leaflet mobility using 4D CT must be performed per the CT Core Laboratory 
(Section 13.3.2) procedure guidelines (see study Manual of Operations). All 4D CT 
scans for subjects enrolled in the CT Imaging Substudy must be sent to the CT Core 
Laboratory for independent analyses.  
Note 3: Images will be read in a standard fashion for cardiac and non-cardiac findings 
by the clinical center CT imaging specialist. Clinical guidelines support anticoagulation 
with warfarin or another vitamin K inhibitor as a Class I recommendation for patients 
with established valve thrombosis4,5. However, there is no established guidance for 
pharmaceutical management of subclinical leaflet thrombosis. If deterioration of 
subject health due to suspected thrombosis occurs, the clinical center may request an 
unblinding of the Core Laboratory findings.  
10.10.2. 6-Month Follow-up (180±30 Days)  
All enrolled subjects must be evaluated 180 (±30) days after the index procedure in person or 
via telehealth. During the 6-month follow-up visit, the following assessments must be 
completed. The ACURATE IDE eCRFs identify the specific data points to be collected. 
• Weight  
• NYHA classification  
• Modified Rankin Scale score, which must be performed by a neurology professional or 
certified personnel (external or internal certification); mRS assessors should be 
independent (not involved with the care of study subjects). 
• 12-lead ECG  

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Note 1:  A 12-lead ECG must be obtained for all subjects, even if the associated follow-
up assessment is carried out via telehealth.       
• Current antiplatelet, anticoagulant (if applicable) medications 
• TTE including assessment of EOA, peak and mean aortic valve gradient pressure, 
aortic regurgitation assessment, mitral regurgitation, LVEF, left ventricular end-
diastolic and end-systolic diameter, TR jet velocity and LA volume.  TTE must be 
performed per the Echocardiography Core Laboratory procedure guidelines (see study 
Manual of Operations). All TTEs for enrolled subjects must be provided to the 
echocardiography core laboratory for independent analyses. 
 
Note 2: TTE must be done for all subjects who have a transcatheter valve implanted in 
the aortic position during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth. Subjects who do not receive a transcatheter 
valve during the index procedure are not required to have follow-up TTE.  
• Complete adverse event (AE, SAE, SADE, UADE, ADE and CEC events) assessment 
for test and control devices and device deficiencies assessment for test device(s), with 
associated treatment 
10.10.3. 1-Year Follow-up (365±30 Days)  
All enrolled subjects must be evaluated 365 (±30) days after the index procedure in person or 
via telehealth. During the 1-year follow-up visit, the following assessments must be 
completed. The ACURATE IDE eCRFs identify the specific data points to be collected. 
• Weight  
• NYHA classification  
• Modified Rankin Scale score, which must be performed by a neurology professional or 
certified personnel (external or internal certification); mRS assessors should be 
independent (not involved with the care of study subjects).  
• NIHSS, which must be performed by a neurology professional or certified personnel 
(external certification); NIHSS assessors should be independent (not involved with the 
care of study subjects). 
• 12-lead ECG 
Note 1:  A 12-lead ECG must be obtained for all subjects, even if the associated follow-
up assessment is carried out via telehealth.     
• Current antiplatelet, anticoagulant (if applicable) medications 
• TTE including assessment of EOA, peak and mean aortic valve gradient pressure, 
aortic regurgitation assessment, mitral regurgitation, LVEF, left ventricular end-
diastolic and end-systolic diameter, TR jet velocity and LA volume.  TTE must be 
performed per the Echocardiography Core Laboratory procedure guidelines (see study 

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Manual of Operations). All TTEs for enrolled subjects must be provided to the 
echocardiography core laboratory for independent analyses. 
 
Note 2: TTE must be done for all subjects who have a transcatheter valve implanted in 
the aortic position during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth. Subjects who do not receive a transcatheter 
valve during the index procedure are not required to have follow-up TTE.  
• Quality of Life Surveys: Kansas City Cardiomyopathy and SF-12 Quality of Life 
Questionnaires 
• Complete adverse event (AE, SAE, SADE, UADE, ADE and CEC events) assessment 
for test and control devices and device deficiencies assessment for test device(s), with 
associated treatment 
• For subjects enrolled in the CT Imaging Substudy, assessment of prosthetic valve 
leaflet mobility using 4D CT must be performed per the CT Core Laboratory procedure 
guidelines (see study Manual of Operations). The 4D CT scans done for the CT 
Imaging Substudy must be sent to the CT Core Laboratory for independent analyses.  
Note 3: Images will be read in a standard fashion for cardiac and non-cardiac findings 
by the clinical center CT imaging specialist. Clinical guidelines support anticoagulation 
with warfarin or another vitamin K inhibitor as a Class I recommendation for patients 
with established valve thrombosis4,5. However, there is no established guidance for 
pharmaceutical management of subclinical leaflet thrombosis. If deterioration of 
subject health due to suspected thrombosis occurs, the clinical center may request an 
unblinding of the Core Laboratory findings.  
10.10.4. Annual Follow-up (±45 Days) to 5 Years 
All implanted subjects must be evaluated in person or by telehealth visit at 2, 3, 4, and 
5 years after the index procedure, with a window of ±45 days. During the annual follow-up, 
the following assessments must be completed. The ACURATE IDE eCRFs identify the 
specific data points to be collected. 
• Weight  
• NYHA classification  
• Modified Rankin Scale score, which must be performed by a neurology professional or 
certified personnel (external or internal certification); mRS assessors should be 
independent (not involved with the care of study subjects). 
• Current antiplatelet, anticoagulant (if applicable) 
• TTE, including assessment of EOA, peak and mean aortic valve gradient pressure, 
aortic regurgitation assessment, mitral regurgitation, LVEF, left ventricular end-
diastolic and end-systolic diameter, TR jet velocity, and LA volume, per the 
Echocardiography Core Laboratory procedure guidelines. All TTEs must be forwarded 
to the core laboratory for independent analyses. 

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Note: TTE must be done for all subjects who have a transcatheter valve implanted in 
the aortic position during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth. Subjects who do not receive a transcatheter 
valve during the index procedure are not required to have follow-up TTE. 
• Complete serious adverse event (SAE, SADE, UADE, and CEC events) assessment for 
test and control devices and device deficiencies assessment for test device(s) with 
associated treatment. 
• Quality of Life Surveys: Kansas City Cardiomyopathy and SF-12 Quality of Life 
Questionnaires at 5 years 
10.10.5. Follow-up (±60 Days) at 7 and 10 Years 
All implanted subjects must be evaluated in person or via telehealth at 7 and 10 years after 
the index procedure, with a window of ±60 days. The following assessments must be 
completed. The ACURATE IDE eCRFs identify the specific data points to be collected. 
• NYHA classification 
• Current antiplatelet, anticoagulant (if applicable)   
• TTE, including assessment of effective orifice area, peak and mean aortic valve 
gradient pressure, aortic regurgitation assessment, peak aortic velocity, and LVEF per 
the Echocardiography Core Laboratory procedure guidelines. All TTEs must be 
forwarded to the core laboratory for independent analyses. 
Note 1: TTE must be done for all subjects who have a transcatheter valve implanted in 
the aortic position during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth.   
• Serious adverse event (SAE, SADE, UADE, and relevant VARC events to be 
adjudicated by the CEC) assessment for test and control devices and device deficiencies 
assessment for test device(s) with associated treatment. 
Note 2: Relevant VARC events to be adjudicated by the CEC include the following: 
mortality, stroke, spontaneous myocardial infarction, acute kidney injury, repeat 
procedure for valve-related dysfunction, hospitalization for valve-related symptoms or 
worsening congestive heart failure (NYHA III or IV), new pacemaker, new onset atrial 
fibrillation or atrial flutter, prosthetic aortic valve malpositioning (valve migration, 
valve embolization, or ectopic valve deployment), TAV-in-TAV, prosthetic aortic 
valve thrombosis and endocarditis. 
10.10.6. Follow-up (±60 Days) at 6, 8 and 9 Years 
All implanted subjects must be evaluated at 6, 8, and 9 years after the index procedure, with a 
window of ±60 days. This evaluation may be conducted by telephone. The following 
assessments must be completed. The ACURATE IDE eCRFs identify the specific data points 
to be collected. 

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• Current antiplatelet, anticoagulant (if applicable)  
• Serious adverse event (SAE, SADE, UADE, and relevant VARC events to be 
adjudicated by the CEC) assessment for test and control devices and device deficiencies 
assessment for test device(s) with associated treatment. Please see Section 10.10.5 for a 
list of relevant VARC events. 
10.11. Study Completion 
All subjects who receive a test or control device will be evaluated at discharge or 7 days 
(whichever comes first), 30 days, 6 months, and then annually up to 10 years post index 
procedure. Visits in the first 5 years and at 7 and 10 years are office/in-person/telehealth 
visits. Evaluations may be conducted by telephone at 6, 8 and 9 years. A subject’s 
participation in the study will be considered complete after the 10-year visit. For subjects 
who do not receive a test or control device, participation in the study will be considered 
complete after the 1-year visit. Any ongoing adverse events after study completion should be 
managed per standard of care. 
Data are collected at each office/in-person/telehealth visit per the data collection schedule in 
Table 10.1-1.  
10.12. Source Documents 
It is preferable that original source documents, when available, are maintained at the 
investigative center. In lieu of original source documents, certified copies are required to be 
maintained. A certified copy is a copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by generation through a validated 
process) to have the same information, including data that describe the context, content, and 
structure, as the original. Source documentation includes but is not limited to those items 
noted in Table 10.12-1. 
Table 10.12-1: Source Documentation Requirements 
Requirement 
Disposition 
Printed, optical, or electronic document containing source data. Examples may include but 
are not limited to: hospital records, laboratory notes, device accountability records, 
photographic negatives, radiographs, records kept at the investigation center, at the 
laboratories and at the medico-technical departments involved in the clinical investigation. 
Retain at center. 
Note: Please see Table 25.2-1 for definitions of “source data” and “source document.” 
 
10.13. Local Laboratory/Vendor Documentation 
Appropriate certifications and documentation records are required to be maintained at the 
investigative center for local laboratory/vendor work.   

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11. Statistical Considerations 
Full methods are described in the Statistical Analysis Plan. 
11.1. Endpoints 
The randomized data from the Main Randomized Cohort of the ACURATE IDE trial will be 
used for primary endpoint analysis.  
Data will be summarized separately for subjects in the ACURATE IDE Roll-In cohort (up to 
170 subjects). Descriptive statistics will be used to summarize these Roll-In cohort data and 
no statistical inference will be made. 
Data will be summarized separately for the specific statistical hypothesis associated with the 
ACURATE Prime™ XL Nested Registry. Descriptive statistics also will be used to 
summarize data from subjects in the single-arm ACURATE Prime XL cohort. 
Data will be summarized separately for subjects in the ACURATE Extended Durability 
Study. Descriptive statistics will be used to summarize these data and no statistical inference 
will be made. 
Data will be summarized separately for subjects in the single-arm ACURATE Continued 
Access Study. Descriptive statistics will be used to summarize these data and no statistical 
inference will be made. 
Event definitions can be found in Table 25.2-1.  
11.1.1. Primary Endpoint 
The primary endpoint is the composite of all-cause mortality, all stroke, and rehospitalization 
at 1 year. The events in this endpoint will be adjudicated by an independent CEC (see 
Section 21.1.1). 
Note 1: For the primary endpoint, rehospitalization is hospitalization for valve-related 
symptoms or worsening congestive heart failure (NYHA class III or IV); per VARC-2 
definition 
11.1.1.1. Statistical Hypothesis for the Primary Endpoint – Main Randomized Cohort 
For the Main Randomized Cohort, the statistical hypothesis is that the primary endpoint 
(composite of all-cause mortality, all stroke, and rehospitalization at 1 year) rate for the 
ACURATE (test) group is non-inferior to that for the Control group. 
The null and alternative hypotheses for the primary endpoint are as follows: 
 
H0: PE_ACURATE minus PE_Control ≥ Δ (Inferior) 
 
H1: PE_ACURATE minus PE_Control < Δ (Non-inferior) 
where PE_ACURATE and PE_Control correspond to the primary endpoint rates for the ACURATE 
and the Control group, respectively, and Δ is the non-inferiority margin. 

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The primary analysis set for the primary endpoint is the ITT analysis set. This endpoint will 
also be analyzed for the implanted analysis set (see Section 11.2.1 for definitions of analysis 
sets). 
A Bayesian analysis28,30 will be performed to estimate the treatment difference between 
ACURATE and Control through posterior probability. Additional information is provided 
below. 
11.1.1.2. Sample Size Parameters for the Primary Endpoint – Main Randomized Cohort 
Although the primary endpoint analysis is performed using the Bayesian method, the sample 
size calculation for the randomized cohort (see Note 2 below) is based on a standard non-
inferiority two-sample test approach. The sample size calculation for the primary endpoint is 
based on the following assumptions. 
• 
Expected rate for both arms = 22.3% (based on a weighted average of TAVR 
data19,22,28-30,34,41,46,51,82; see Note 3 below) 
• 
Non-inferiority margin (Δ) = 8.0% (36% relative to expected rate) 
• 
Test significance level (α) = 0.025 (1-sided) (see Note 4 below) 
• 
Test (ACURATE): Control ratio = 1:1 
• 
Power (1 minus ß) > 90% 
• 
Expected rate of attrition = 5% 
• 
Total sample size = 1500 (750 per group) 
• 
Number of evaluable subjects per group = 712 
• 
Analyses: One administrative, one formal interim, one final (see Note 5 and Note 6 
below) 
Note 2: The Pocock-type method83 is used for sample size calculations. The statistical 
software EAST® 6.584 is used for the sample size calculations. 
Note 3: The estimated proportions of subjects in the Main Randomized Cohort by operative 
risk level are 10% extreme risk, 25% high risk, 30% intermediate risk, and 35% low risk. 
Note 4: A statistically equivalent posterior probability threshold for the Bayesian analysis is 
empirically chosen through extensive simulations and is pre-specified in the Statistical 
Analysis Plan (SAP). 
Note 5: The administrative interim analysis will be conducted when the first 350 Main 
Randomized Cohort subjects have completed 1-year follow-up. The formal interim analysis 
will be carried out after enrollment in the Main Randomized Cohort is completed. This 
formal interim analysis will be conducted on the full N=1500 subject cohort of the Main 
Randomized Cohort after the first 1050 subjects in the Main Randomized Cohort have 
completed 1-year follow-up. The piecewise exponential model30 based on outcomes among 
these subjects will be used to predict the 1-year results by treatment group for the remaining 
enrolled subjects. The Bayesian method will be used to perform the hypothesis testing on the 
combined data sets. A final analysis will be performed on all subjects with completed 1-year 
data if non-inferiority cannot be claimed at the formal interim analysis (see Section 11.1.1.3). 

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Note 6: Analyses of the Extended Durability Study and the ACURATE CAS are not 
expected to occur when the formal interim analysis is performed on the Main Randomized 
Cohort. See Section 11.1.2 below for information on analyses associated with the 
ACURATE Prime XL cohort.   
11.1.1.3. Success Criteria for the Primary Endpoint – Main Randomized Cohort 
The Bayesian method is used to test the non-inferiority hypothesis of the primary endpoint. 
To establish that the ACURATE device is non-inferior to the Control, the results will need to 
meet the following equation: 
Pr(H1 | Data) > ξ   
where  
• Pr(H1 | Data) is the posterior probability of H1 given the observed data at either the 
interim or the final analysis;  
• H1 is the alternative hypothesis for non-inferiority: PE_ACURATE  minus PE_Control < Δ; 
• ξ is a prespecified threshold, which is empirically chosen through extensive simulations 
using the Bayesian approach for the non-inferiority tests.  
If non-inferiority has been declared at the formal interim analysis, the non-inferiority test will 
not be performed at the final analysis. If non-inferiority cannot be declared at this interim 
analysis, the non-inferiority test will be performed at the final analysis for all subjects using 
the Bayesian method with the same pre-specified threshold. The study will not stop for 
futility at the interim analysis. 
The detailed study operating characteristics and simulation results will be provided in the 
SAP. 
11.1.1.4. Statistical Methods – Primary Endpoint – Main Randomized Cohort 
All subjects who are enrolled and randomized will be eligible for evaluation. Any events or 
hospitalizations occurring after enrollment but prior to the index procedure should be entered 
in the electronic data capture system.  
Handling of dropouts and missing data will depend on their frequency and the nature of the 
outcome measure. Sensitivity analyses (e.g., tipping-point analysis) will be performed to 
assess the impact of subjects with inadequate follow-up (i.e., missing data) on the primary 
endpoint and to assess the robustness of the conclusion of the primary analysis. A sensitivity 
analysis of the primary endpoint, including events occurring after enrollment but prior to the 
index procedure, will be performed. Statistical models that account for censored data will be 
employed in appropriate circumstances (e.g., for time-to-event outcomes). Suspected invalid 
data will be queried and corrected in the database prior to statistical analysis. Additional 
information may be found in the SAP. Please also see Section 9.4, Section 10.1, and 
Section 10.2.1 regarding data collection and missing data.  

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11.1.2. ACURATE Prime XL Nested Registry Statistical Assessment 
The statistical assessment for the ACURATE Prime XL Nested Registry is summarized in 
the sections below. Additional information may be found in the SAP. 
11.1.2.1. Statistical Hypothesis – ACURATE Prime XL Nested Registry 
The statistical hypothesis is that the mean aortic valve pressure gradient at 30 days post 
implant procedure is less than a performance goal (PG): 
 
H0: Gradient30D ≥ PG 
 
H1: Gradient30D < PG 
where Gradient30D is the 30-day mean aortic valve pressure gradient for the ACURATE 
Prime XL valve and PG is 15 mmHg. 
A one-sample t-test will be used to test the one-sided hypothesis at a significance level of 
2.5%. 
11.1.2.2. Sample Size Parameters for the ACURATE Prime XL Nested Registry  
The sample size calculation is based on the following assumptions. 
• Expected 30-day mean pressure gradient from ACURATE Prime XL = 10 mmHg 
• Expected standard deviation = 7 mmHg  
• PG = 15 mmHg 
• Test significance level (α) = 0.025 (1-sided) 
• Power > 90% 
• Evaluable number of subjects = Minimum of 40 subjects 
• Expected rate of attrition = 20% (8 subjects) 
• Planned enrollment of 50 subjects  
• The analysis population for the hypothesis testing will be the subject population 
implanted with the ACURATE Prime XL valve.   
Note: The expected mean gradient is based on Boston Scientific data on file and published 
data for large-annulus CoreValve devices43,48,49.   
11.1.2.3. Success Criteria for the ACURATE Prime XL Nested Registry  
If the P value from the one-sample t-test is < 0.025, the ACURATE Prime XL valve will be 
concluded to have a 30-day mean aortic valve pressure gradient < 15 mmHg. This 
corresponds to the one-sided upper 2.5% confidence bound of the observed 30-day mean 
aortic valve pressure gradient being < 15 mmHg. 

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11.1.3. Baseline Comparability 
Baseline data will be summarized by treatment group for the randomized subjects (Main 
Randomized Cohort and Extended Durability Study) and separately for the Roll-In, 
ACURATE Prime XL Nested Registry, and CAS subjects. Subject demographics, clinical 
and neurological history, risk factors, and pre-procedure characteristics will be summarized 
using descriptive statistics (e.g., mean, standard deviation, n, minimum, maximum) for 
continuous variables and frequency tables or proportions for discrete variables. Treatments 
for the randomized subjects will be compared with a chi-square or Fisher exact test for 
discrete variables and a Student t-test for continuous variables. Procedural characteristics will 
be summarized similarly. No formal statistical testing will be done for the Roll-In, Extended 
Durability, or CAS subjects. Please see Section 11.1.2 regarding statistical testing for the 
ACURATE Prime XL Nested Registry. 
11.1.4. Post-procedure Measurements 
Post-procedure information will be collected at regularly scheduled follow-up examinations 
as detailed in the clinical study schedule (Table 10.1-1) and will be summarized using 
descriptive statistics for continuous variables (e.g., mean, standard deviation, n, minimum, 
maximum) and frequency tables or proportions for discrete variables. Estimates will be 
reported by treatment group and, for randomized subjects (Main Randomized Cohort and 
Extended Durability Study), differences between treatment groups and their 95% confidence 
intervals will be presented. Treatments for the randomized subjects will be compared with 
the chi-square or Fisher exact test for discrete variables and the Student t-test for continuous 
variables. No inferences are planned on the additional measurements and, therefore, alpha-
adjustments for multiple comparisons will not be used. The Kaplan-Meier product-limit 
method will be used to estimate rates for time-to-event endpoints and treatment groups will 
be compared using the Log-rank and Wilcoxon tests. Adverse event and SAE rates will be 
reported. No formal statistical testing will be done for the Roll-In, Extended Durability 
Study, or ACURATE CAS subjects. Please see Section 11.1.1.1 and Section 11.1.2, 
respectively, regarding statistical testing for the Main Randomized Cohort and the 
ACURATE Prime XL Nested Registry. 
11.2. General Statistical Methods 
All statistical analyses will be performed using the SAS System software, version 9.2 or later 
(Copyright© 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, USA. 
All rights reserved).  
All statistical analyses will be conducted according to applicable Standard Operating 
Procedures, Work Instructions, and the study-specific SAP. 
11.2.1. Analysis Sets 
The primary endpoint and additional measurements will be analyzed on an ITT and an 
implanted basis.  

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Subjects in the randomized cohorts (Main Randomized Cohort and Extended Durability 
Study) are considered enrolled in the study upon randomization. Among the randomized 
cohorts, for ITT analyses, all subjects who sign the IRB/REB/HREC/ IEC-approved study 
ICF (see Section 10.3), are enrolled in the trial, and are randomized will be included in the 
analysis, whether or not an assigned study valve (ACURATE or Control) was implanted. For 
implanted analyses, ITT subjects who had the assigned (Test versus Control), randomized 
study valve implanted will be included in the analysis.  For the implanted randomized cohort 
analysis sets, if a subject receives 2 different valve types from 2 different manufacturers, the 
subject will be excluded from the implanted analysis. 
With the Roll-In, ACURATE Prime™ XL Nested Registry, and ACURATE CAS cohorts, 
the subject is considered enrolled in the trial when there is an attempt made to insert the 
ACURATE Transfemoral Aortic Valve System into the subject’s femoral artery. For ITT 
analyses, all subjects who sign the IRB/REB/HREC/IEC-approved study ICF and are 
enrolled in the trial will be included in the analysis sample, regardless of whether the study 
device was implanted. The implanted population includes all subjects who sign an ICF and 
are implanted with an ACURATE valve.  
For the Main Randomized Cohort, the primary endpoint will be analyzed for the ITT and 
implanted analysis sets. The primary analysis for the primary endpoint will be based on the 
ITT analysis set.  
11.2.2. Control of Systematic Error/Bias 
All subjects who have met the inclusion/exclusion criteria, received a positive 
recommendation from the CRC, and signed the Informed Consent Form will be eligible for 
enrollment in the study. The center heart team’s assessment of TTE measurements before 
device placement will contribute to the determination of subject eligibility for the study.  
To control for inter-observer variability, data from independent core laboratories (see 
Section 13.3) will be used for analysis. These include an echocardiography core laboratory 
and a CT/Angiography core laboratory to assess all data using standard techniques. Clinical 
endpoints will also be adjudicated by an independent CEC (Section 21.1.1). 
11.2.3. Number of Subjects Per Investigative Center 
The number of subjects enrolled per investigational center should not exceed 180 without 
prior authorization by the sponsor. 
11.2.4. Randomization Scheme 
For the Main Randomized Cohort and Extended Durability Study, a computer-generated list 
of random treatment allocations (i.e., a randomization schedule) will be used to assign 
subjects in the ACURATE IDE trial to treatment in a 1:1 ratio of ACURATE  to Control. 
Randomization will be stratified by center and by intended control device. Additional 
information is provided in the study Manual of Operations. 

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11.2.5. Reporting Events 
For all subjects in the ACURATE IDE Roll-In, ACURATE Prime™ XL Nested Registry, 
and ACURATE CAS cohorts, all events that occur from the time of enrollment will be 
reported. For all subjects in the ACURATE IDE randomized cohorts (Main Randomized 
Cohort and Extended Durability Study), events from the time of randomization onward will 
be reported.  
For randomized subjects who do not have an attempted procedure, events from the date of 
randomization to 1-year post-randomization will be reported. For subjects who are enrolled 
and have an attempted procedure but do not receive a study valve, events from the index 
procedure to 1-year post procedure will be reported.  
For time-based clinical events, the cut-off for events for 30-day endpoints will be 30 days, 
for 6-month endpoints it will be 180 days, for 1-year endpoints it will be 365 days, and for 
endpoints at 2–10 years it will be 365 days times the number of years. For events at discharge 
or 7 days post-procedure, the cut-off for events will be the earlier of the date of discharge or 
7 days post-procedure for each subject. 
11.3. Data Analyses 
Baseline and outcome variables will be summarized using descriptive statistics for 
continuous variables (mean, standard deviation, number of observations, minimum and 
maximum) and discrete variables (percentage and count/sample). See Section 11.1 for a 
discussion on analysis of the primary endpoint and additional measurements. 
11.3.1. Other Measurements  
Other measurements not driven by statistical hypotheses are listed in Section 6.4. 
11.3.2. Interim/Administrative Analyses  
There will be 2 interim analyses as described in the SAP. The administrative interim analysis 
will be conducted when the first 350 subjects in the Main Randomized Cohort have 
completed 1-year follow-up visits. The formal interim analysis will be carried out after 
enrollment in the Main Randomized Cohort is completed (see Note 1 below). This formal 
interim analysis will be conducted on all (N=1500) Main Randomized Cohort subjects after 
the first 1050 Main Randomized Cohort subjects have completed 1-year follow-up. The 
piecewise exponential model30 based on outcomes among these subjects will be used to 
predict the 1-year results by treatment group for the remaining enrolled subjects. The 
Bayesian method will be used to perform the hypothesis testing on the combined data sets. A 
final analysis will be performed on all subjects in the Main Randomized Cohort with 
completed 1-year data if non-inferiority cannot be claimed at the formal interim analysis (see 
Section 11.1.1.3). Additional information may be found in the SAP.  
A Data Monitoring Committee (DMC; Section 21.1.2) will monitor safety events. The DMC 
reports will be generated according to the DMC charter. 

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Note 1: Analyses of the Extended Durability Study and the ACURATE CAS are not 
expected to occur when the formal interim analysis is performed on the Main Randomized 
Cohort. See Section 11.1.2 for information on analyses associated with the ACURATE 
Prime XL cohort.  
11.3.3. Subgroup Analyses for Main Randomized Cohort Subjects 
Primary and pre-specified additional endpoints will be summarized for the following 
subgroups of the Main Randomized Cohort as described in the SAP.  
• Gender (male and female) 
• Valve type (ACURATE neo2, SAPIEN, CoreValve) 
• Age (< 75 years and ≥ 75 years) 
• Any race and ethnicity category with >100 enrolled subjects as described in the SAP 
• Valve size (Small, Medium, Large) 
• Operative risk (low, intermediate, high/extreme) 
Treatment groups will also be compared in the age, race, and gender subgroup analyses. No 
adjustments for multiple comparisons will be made. Additional analyses may be performed 
as appropriate. 
In the 4D CT Imaging Substudy, computed tomography data will be analyzed after 200 
subjects have reached 1-year follow-up.  
11.3.4. Justification of Pooling 
Analyses for the primary endpoint in the Main Randomized Cohort will be presented using 
data pooled across study centers. Poolability analyses across study centers will be performed 
for the primary endpoint. The differences of treatment effects on the primary endpoint across 
study centers will be examined using the interaction term from logistic regression models. 
Please see the SAP for additional information.  
11.3.5. Multivariable Analyses 
Univariate and multivariate analyses will be performed to assess the effect of potential 
predictors on the primary endpoint in the Main Randomized Cohort as described in the SAP. 
11.3.6. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended SAP approved before performing the analyses. Changes from the 
planned statistical methods after performing the analyses will be documented in the clinical 
study report along with a reason for the deviation. 

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12. Health Economics Outcomes 
A formal health economics analysis may be completed as part of this trial, provided 
meaningful clinical results are obtained. This will take into consideration any differences in 
mortality, event rates, quality of life, and resource utilization. Quality of life will be 
evaluated by the Kansas City Cardiomyopathy71 and SF-1272 questionnaires at baseline, 
1 month, 1 year, and 5 years. These inputs may be used in any health economics analysis 
performed. 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system. Only personnel trained and authorized will have access to the system. 
The clinical database will reside on a production server hosted by Medidata EDC System 
(New York, NY, USA). All changes made to the clinical data will be captured in an 
electronic audit trail and made available for review by the Sponsor or its representative. The 
associated RAVE software and database have been designed to meet regulatory compliance 
for deployment as part of a validated system compliant with laws and regulations applicable 
to the conduct of clinical studies pertaining to the use of electronic records and signatures. 
Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the Sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the center for appropriate response. Center staff will be responsible for 
resolving all queries in the database.  
All access to the clinical database will be changed to “Read Only” after all data are either 
“Hard Locked” or “Entry Locked.” Once acceptance of the final study report or finalization 
of publications (as applicable) is received, final database storage and archiving activities can 
begin. When all closeout activities are completed, a request to the BSC Information 
Technology department is submitted to have the database locked or decommissioned and all 
database access revoked. 
13.2. Data Retention 
The Principal Investigator or his/her designee or Investigational center will maintain all 
essential study documents and source documentation that support the data collected on the 

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study subjects in compliance with applicable regulatory requirements. Documents must be 
retained for at least 2 years after the last approval of a marketing application or until at least 
2 years have elapsed since the formal discontinuation of the clinical investigation of the 
product. These documents will be retained for a longer period of time by agreement with 
BSC or in compliance with other local regulations.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Centers are required to inform BSC in writing 
where paper or electronic files are maintained in case files are stored off site and are not 
readily available. 
13.3. Core Laboratories 
13.3.1. Echocardiography Core Laboratory 
An independent core laboratory will review echocardiography images from all centers and 
every subject enrolled in this study for qualitative and quantitative analysis. These analyses 
will minimize bias and inconsistencies by providing an independent interpretation of all 
measurements using standard techniques. The TTE procedure guideline is provided by the 
core laboratory in the study Manual of Operations.  
13.3.2. CT and Angiography Core Laboratory 
An independent core laboratory will centrally assess all of the CT and angiography data in 
this study to reduce variability. These analyses will minimize bias and inconsistencies by 
providing an independent interpretation of all measurements using standard techniques.  
Procedure guidelines are provided by the core laboratory in the study Manual of Operations. 
Data from subjects in the 4D CT Imaging Substudy will also be evaluated by the independent 
CT core laboratory; procedure guidelines for 4D CT scanning are provided by the core 
laboratory in the Manual of Operations. 
13.3.3. Histopathology Core Laboratory 
If an ACURATE valve (test device) is explanted during conventional scheduled or emergent 
surgical valve replacement or during an autopsy, please refer to the study Manual of 
Operations for recommendations on the explant procedure and shipment of the explanted 
valve for assessment by an independent histopathology laboratory. 
14. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 

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Sponsor and the reviewing IRB/REB/HREC/IEC of any deviation from the investigational 
plan to protect the life or physical well-being of a subject in an emergency, and those 
deviations which affect the scientific integrity of the clinical investigation. Such notice shall 
be given as soon as possible, but no later than 5 working days after the emergency occurred, 
or per prevailing local requirements, if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using the EDC CRF. Centers 
may also be required to report deviations to the IRB/REB/HREC/IEC, per local guidelines 
and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/REB/HREC/IEC notification, center re-
training, or center discontinuation/termination) will be put into place by the Sponsor. 
The sponsor will not approve protocol waivers.  
15. Device Accountability  
15.1. Device Accountability for Products Labelled Investigational 
The investigational devices shall be securely maintained, controlled, and used only in this 
clinical study. Additionally, study personnel must follow the instructions related to the 
storage of the test device as noted in the corresponding clinical DFU/IFU. An electronic 
interactive response technology (IRT) will be used for investigational device management 
and accountability during the study.  
The Sponsor or designee shall keep records to document the physical location of all 
investigational devices from shipment of the investigational devices from BSC or a 
designated facility to the investigation centers until return or disposal. The IRT will be used 
to document reception of the investigational device at a center. Records shall be kept by 
authorized center study personnel to document the physical location and conditions of 
storage of all investigational devices. Centers must not dispose of any investigational devices 
for any reason at the center unless instructed to do so by BSC. Any investigational device 
that is disposed of at the center must be documented appropriately. Centers must document 
the reasons for any discrepancy noted in device accountability. 
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return, transfer, and disposal of the investigational devices, which shall include 
the following. 
• Date of receipt at the center 
• Identification of each investigational device (unique identifier or lot number/batch 
number/serial number, valve size) 
• Expiry date, as applicable 
• Date of use 

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• Subject identification 
• Date on which the investigational device was explanted from subject/returned, if 
applicable 
• Date of return and quantity of all investigational devices, as applicable. 
Note: Written procedures may be required by national regulations.  
Once the Investigator and center are notified in writing by BSC that subject enrollment is 
complete, all unused investigational devices must be returned to BSC or its designee. 
15.2. Device Accountability for the Control Device 
Appropriate information on the control device size and model will be collected.  
16. Compliance 
16.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site 
can be “Authorized to Enroll,” the investigational site must enter into a Clinical Study 
Agreement with the sponsor that details the financing of the study as well as the rights and 
obligations of the investigational site and the investigator. 
This study will be conducted in accordance with 21 CFR 814.20 Parts 11, 50, 54 56, 812, 
813; the relevant parts of the International Conference on Harmonisation (ICH) Guidelines 
for Good Clinical Practices (GCP) or the International Standard ISO 14155: Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical Practice; ethical 
principles that have their origins in the Declaration of Helsinki; and applicable individual 
country laws and regulations. The study shall not begin until the required approval/favorable 
opinion from the IRB/REB/HREC/IEC and/or regulatory authority has been obtained, if 
appropriate. Also, the study shall not begin prior to issuance of the center Authorization to 
Screen, as provided by the Sponsor. Any additional requirements imposed by the IRB/REB/ 
HREC/IEC or regulatory authority shall be followed, if appropriate.   
16.2. Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the clinical 
investigation plan/protocol, ISO 14155 or ICH/GCP, ethical principles that have their origins 
in the Declaration of Helsinki, any conditions of approval imposed by the reviewing 
IRB/REB/HREC/IEC, and prevailing local and/or country laws and/or regulations, 
whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  

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• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement. 
• Prior to beginning the study, sign the Investigator Brochure Signature Page and 
Protocol Signature page documenting his/her agreement to conduct the study in 
accordance with the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the center team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Complete training requirements associated with the Control device(s). 
• Complete all ACURATE Transfemoral Aortic Valve System (investigational device) 
training requirements as detailed in the ACURATE IDE Training Plan (Section 16.4.2). 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
Sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to BSC, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB/REB/HREC/IEC and regulatory authorities any SAEs and device 
deficiencies that could have led to a SADE and potential/USADE or UADE, if required 
by applicable laws or regulations or this protocol or by the IRB/REB/HREC/IEC, and 
supply BSC with any additional requested information related to the safety reporting of 
a particular event. 
• Maintain the device accountability records and control of the investigational device, 
ensuring that the investigational device is used only by authorized/designated users and 
in accordance with this protocol and instructions/directions for use. 
• Allow the Sponsor and Sponsor representatives to perform monitoring and auditing 
activities and be accessible to the clinical research monitor or auditor and respond to 
questions during monitoring visits or audit(s). 
• Allow and support regulatory authorities and the IRB/REB/HREC/IEC when 
performing auditing activities. 

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• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/REB/HREC/IEC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation (e.g., 
implant card), together with identification and compliance information for concomitant 
treatment measures (contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation center team and facilities exist and are maintained 
and documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks through up-to-date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that may interfere with the conduct 
of the clinical study or interpretation of results. 
16.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, so the delegate is competent to perform the tasks they have been 
delegated, and adequate supervision of those to whom tasks are delegated. Where there is a 
sub-investigator at a center, the sub-investigator should not be delegated the primary 

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supervisory responsibility for the center. The investigator is accountable for regulatory 
violations resulting from failure to adequately supervise the conduct of the clinical study.  
16.3. Institutional Review Board/Research Ethics Board/Human Research Ethics 
Committee/ Independent Ethics Committee 
The investigational center will obtain the written and dated approval/favorable opinion of the 
Institutional Review Board/Research Ethics Board/Human Research Ethics Committee/ 
Independent Ethics Committee (IRB/REB/HREC/IEC) for the clinical investigation before 
recruiting subjects and implementing all subsequent amendments, if required. 
A copy of the written IRB/REB/HREC/IEC approval of the protocol (or permission to 
conduct the study) and ICF, must be received by the Sponsor before recruitment of subjects 
into the study and shipment of investigational product. Prior approval must also be obtained 
for other materials related to subject recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/REB/HREC/ 
IEC before the changes are implemented to the study. All changes to the ICF will be 
IRB/REB/HREC/IEC approved; a determination will be made regarding whether a new ICF 
needs to be obtained from subjects who provided consent, using a previously approved ICF. 
Annual IRB/REB/HREC/IEC approval and renewals will be obtained throughout the 
duration of the study as required by applicable local/country laws or regulations or IRB/REB/ 
HREC/IEC requirements. Copies of the study reports and the IRB/REB/HREC/IEC 
continuance of approval must be provided to the Sponsor.  
16.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to, a Contract Research Organization will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research, and proposals for developing new medical products and procedures. All data used 
in the analysis and reporting of this study or shared with a third-party researcher will be 
without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1. Role of Boston Scientific Corporation Representatives 
Boston Scientific personnel (including field clinical engineers) who are trained in the use of 
the investigational device will provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during ACURATE valve preparation and 

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implant and testing required by the protocol. Boston Scientific Corporation (BSC) is also 
responsible for ensuring investigators are trained on the investigational device DFU/IFU. 
Support may include HCP training (see Section 16.4.2 below), addressing HCP questions, or 
providing clarifications to HCPs concerning the operation of BSC equipment/devices.  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the investigator.  
• Independently collect critical study data (defined as primary or secondary endpoint 
data) 
• Enter data in electronic data capture systems or on paper case report forms 
16.4.2. Training with the Investigational Device 
The Sponsor is responsible for providing investigators with the information and training on 
the investigational device they need to conduct the study properly. The Sponsor is 
responsible for maintaining documentation of attendance at each of the training sessions 
provided.  
The ACURATE Healthcare Personnel (HCP) Training Plan developed for this study meets 
the requirements of ISO 5840-3 and includes the following elements.  
• Device Description: A detailed description of all components of the device including a 
summary of the basic principle of operation. 
• Patient Selection and Sizing: A detailed review of pre-procedural imaging techniques to 
aid in patient selection and sizing decisions for valve implantation. 
• Step by Step Procedure: A detailed description of each step of the procedure. The 
training describes any warnings associated with any steps, and tips and tricks for valve 
implantation. 
• Implantation Techniques: A detailed review of specific implantation techniques based 
on clinical cases. 

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• Device Demonstration: A live or hands-on training to simulate/practice the 
implantation procedure with demonstration devices or in a bench model or a robotic 
simulation system. 
• Proctoring: The investigator and co-investigators as well as the scrub team will be 
proctored by an individual experienced with the ACURATE valve and TAVR on a 
minimum of 4 implantation procedures. These are to be performed in the investigator’s 
institution with his/her staff. If the proctor or investigators are not satisfied that these 
initial proctored procedures are sufficient preparation, then subsequent proctoring 
sessions may be added as needed.  
Note 1: The training requirements listed above apply to centers that do not have any previous 
experience implanting the ACURATE neo2 valve. If the center has prior experience 
implanting the ACURATE neo bioprosthesis but does not have experience with the 
ACURATE neo2 Transfemoral Aortic Valve System, the training will be modified to focus 
on the changes between the two. These ACURATE-experienced physicians will not be 
certified to the ACURATE neo2 Transfemoral Aortic Valve System until these training 
requirements have been met and 2 implants with the ACURATE neo2 Transfemoral Valve 
System have been completed.  
Note 2: For centers that do not have implantation experience with the ACURATE neo 
bioprosthesis (transfemoral delivery), at least 2 Roll-In cases will be performed before 
treatment can commence in the randomized cohort. For centers that do not have any previous 
experience implanting the ACURATE neo bioprosthesis, the Roll-In subjects will be treated 
under the supervision of a proctor and will count towards the 4 required proctored cases. 
Centers with prior experience with the ACURATE bioprosthesis who are proctor-free are not 
required to do Roll-In cases but may do Roll-In subjects without the presence of a proctor. 
Note 3: Centers will receive additional training on the ACURATE Prime investigational 
device. An experienced BSC representative will provide technical support as needed during 
valve preparation and implantation. 
16.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage by BSC for 
subjects in the study will be obtained. 
17. Monitoring 
Monitoring will be performed during the study according to the monitoring plan to assess 
continued compliance with the protocol and applicable regulations. In addition, the clinical 
research monitor verifies that study records are adequately maintained, that data are reported 
in a satisfactory manner with respect to timeliness, adequacy, and accuracy, and that the 
Principal Investigator continues to have sufficient staff and facilities to conduct the study 
safely and effectively. The Principal Investigator/institution guarantees direct access to 

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original source documents by BSC personnel, their designees, and appropriate regulatory 
authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements.  
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
18. Potential Risks and Benefits 
Risks to clinical subjects associated with their participation in this clinical investigation, 
arising from the clinical procedures set out in the study protocol, have been identified from 
prior studies conducted by Boston Scientific Corporation and review of relevant literature, 
most recently from the Edwards Lifesciences’ Placement of Aortic Transcatheter Valves 
(PARTNER) trial8,17,19,20, the PARTNER II trial (RCT and SAPIEN 3 intermediate risk 
arm)27,34,40, the PARTNER 329 trial, the SAPIEN 3 CE Mark study85, the CoreValve Extreme 
Risk study41, the CoreValve High Risk Study22, the Evolut R CE Mark study42, the Surgical 
Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial28, the CoreValve 
Low Risk trial30, the EVOLUT R US study44, the PORTICO Pre-CE Mark study45, and the 
PORTICO IDE randomized trial/RESOLVE registry/SAVORY registry86.   
Benefits to subjects anticipated to arise from the use of the investigational device have also 
been identified. These clinical risks and benefits are summarized below, with an assessment 
of the balance of risks and benefits to subjects. Potential risks and benefits have been 
included in the study-specific template of the ICF provided to the study centers (see 
Section 20).  
18.1. Anticipated Adverse Events and Risks Associated with Transcatheter Aortic Valve 
Replacement  
Adverse events (in alphabetical order) potentially associated with TAVR (including, but not 
limited to, standard cardiac catheterization and BAV) as well as additional risks related to the 
use of the investigational and control devices include but may not be limited to the risks 
listed in Table 18.1-1 below. As a result of these complications, the subject may require 
medical, percutaneous, or surgical intervention, including re-operation and replacement of 
the implanted valve. Such complications can be fatal.   
As the ACURATE Transfemoral Valve System is an investigational device, uncertainty 
remains over risks of experiencing some or all of the complications listed below. There may 
be risks that are unknown at this time. 

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Table 18.1-1: Risks Associated with Transcatheter Aortic Valve Replacement 
Abnormal lab values (including anemia and electrolytes) 
Abnormal pressure gradient 
Allergic reaction (including to medications, anesthesia, contrast, or device materials) 
Aneurysm (cardiovascular) 
Angina 
Arrhythmia or new conduction system injury (including need for pacemaker insertion) 
Bleeding or hemorrhage (possibly requiring transfusion or intervention) 
Cardiac arrest 
Cardiac failure/low cardiac output 
Cerebrovascular accident, stroke or transient ischemic attack  
Coronary obstruction 
Death  
Device embolization, misplacement or migration 
Emboli (including air, calcium, tissue, thrombus or device materials)  
Emergency cardiac surgery 
Endocarditis 
Fever 
Heart failure 
Hematoma or lymphatic problems or other complications at the access sites 
Hemodynamic instability or shock 
Hemolysis and/or hemolytic anemia 
Hypertension/hypotension  
Infection (local and/or systemic, including septicemia) 
Inflammation 
Mitral valve insufficiency or injury 
Myocardial infarction or ischemia  
Myocardial or valvular injury (including perforation or rupture) 
Nerve injury 
Non-structural valve dysfunction including implant distortion, improper deployment or sizing 
Pain 
Pericardial effusion or cardiac tamponade 
Peripheral ischemia or infarction 
Permanent disability 
Pleural effusion 
Pulmonary edema 
Radiation injury 
Renal insufficiency or failure 
Respiratory insufficiency or failure 
Thrombosis/thromboembolism 
Valve dysfunction, deterioration or failure 
Valve-in-valve (need for additional valve within a valve) 
Valve or device thrombosis 

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Table 18.1-1: Risks Associated with Transcatheter Aortic Valve Replacement 
Valvular stenosis or regurgitation (central or paravalvular) 
Vessel injury (including spasm, trauma, dissection, perforation, rupture, arteriovenous fistula, acute coronary 
occlusion, or pseudoaneurysm)  
Wound healing disorders 
Note: Risks are listed in alphabetical order. 
 
18.1.1. Reduced Leaflet Motion/Leaflet Thrombosis 
Reduced leaflet motion (RLM) suggestive of subclinical leaflet thrombosis, as detected by 
high-resolution CT, has been reported with bioprosthetic TAVR and SAVR valves86-89. It is 
less common among subjects receiving anticoagulant therapy and, in some cases, has been 
shown to resolve with such treatment86-92.   
Clinical signs of RLM include elevation of transvalvular gradients (as determined by 
echocardiography), central or peripheral thromboembolic events, and unexpected recurrence 
of heart failure. Computed tomography imaging is recommended to appropriately assess 
subjects with echocardiographic and/or clinical suspicion of leaflet thrombosis. Additional 
anticoagulant therapy may be indicated based on symptoms or signs and subject bleeding 
risk86-92.    
The subset of subjects undergoing 4D CT scans at 30 days and 1 year will be exposed to an 
additional radiation dose of about 20 milliSieverts (mSv) which is equivalent to about 10 
years’ worth of natural background radiation. The contrast dye used during the image 
acquisition can cause medical problems such as allergic reactions and increase the risk of 
worsening kidney function or failure.  
18.2. Risks Associated with the Study Device(s)  
Overall, there are no incremental risks expected with the investigational device compared to 
similar devices on the market. 
18.3. Risks Associated with Participation in the Clinical Study 
Risks associated with TAVR and participation in this clinical study are listed above in Table 
18.1-1. 
18.4. Possible Interactions with Concomitant Medical Treatments 
Medications to be used in ACURATE IDE constitute standard of care for TAVR as described 
in society guidelines4,5. Please also see Section 10 for medications to be used in this study. 

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18.5. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
Boston Scientific Corporation will employ measures throughout the course of this 
investigation consistent with the best practices and lessons learned from other ongoing 
TAVR trials and commercial use to minimize risk for subjects choosing to participate. All 
efforts will be made to minimize risks by selecting centers that are experienced and skilled in 
TAVR procedures.  
Risk mitigation will be accomplished through the following actions. 
• Clearly defining the inclusion/exclusion criteria to ensure only appropriate subjects are 
enrolled  
• Confirmation of eligible subjects by a Case Review Committee, including experienced 
investigators in TAVR 
• Ensuring that treatment and follow-up of the subject are consistent with current medical 
practices 
• Selection of investigators who are experienced and skilled in TAVR procedures 
• Completion of training and proctorship provided by the Sponsor  
• Performing all procedures in accordance with the DFU/IFU, including the preparation 
of the valve and delivery system 
• Dynamic safety review processes, including assessment by the Data Monitoring 
Committee (DMC, Section 21.1.2) and CEC (Section 21.1.1) adjudication of specified 
events as recommended by VARC66,67. 
The ACURATE valve has a number of features that help minimize risk (see Section 5.1 for a 
description of the investigational device). The valve is released first at the top and last at the 
inflow; this top-down deployment allows for implantation with minimal protrusion into the 
left ventricular outflow tract. The upper crown opens first to provide stable positioning and 
supra-annular anchoring of the valve, capping the native leaflets and mitigating the risk of 
coronary obstruction. Subsequently, the flexible stabilization arches open to promote valve 
self-alignment and achieve coaxial alignment. The lower crown is then opened to anchor the 
device inside the annulus. The double porcine pericardium skirt sutured on the inner and 
outer surface of the valve stent is also designed to minimize paravalvular leakage with the 
ACURATE neo2 and ACURATE Prime™ XL valves.  
Anticoagulation medication (e.g., heparin) will be administered during the procedure to 
reduce the risk of embolism and stroke. Additionally, post-procedure antiplatelet therapy is 
recommended to minimize any risk of thrombus formation, stroke, or transient ischemic 

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attack. Neurological assessments (NIHSS and mRS) will be performed at each required 
follow-up visit to identify any change in the neurological status of the subjects as 
recommended by VARC66,67. 
Cardiac enzyme measurements as well as ECGs post-procedure will be performed to detect 
periprocedural MI.  
Subjects will be carefully monitored during the procedure, hospitalization, and throughout 
the follow-up period. Serial echocardiograms and electrocardiograms will be used to evaluate 
valve and general cardiac function. Any abnormal rhythm will be assessed and, if needed, the 
implantation of a permanent pacemaker will be performed.  
Subjects who are converted to standard surgical aortic valve replacement will be carefully 
monitored in a method appropriate for their surgical procedure.   
Data will be monitored as they are submitted to BSC. Qualified employees of BSC, or a 
designee under contract, will conduct monitoring visits at the initiation of the study and at 
interim intervals described in the monitoring plan throughout the course of the study to 
evaluate protocol compliance and determine if there are any issues that could affect the safety 
or welfare of any subject in the study. 
18.6. Anticipated Benefits 
18.6.1. Potential Benefits to the TAVR Procedure 
Transcatheter aortic valve replacement (TAVR) may offer certain advantages when 
compared to surgical replacement of the stenotic aortic valve. Known benefits associated 
with TAVR, as described in the scientific literature (see summary in Section 4.1.2 of this 
document and details in the IB), potentially include the following. 
• Minimally invasive procedure and reduced risks related to open heart surgery 
• Shorter stay in the intensive care unit and overall hospital stay 
• Reduced blood loss 
• More rapid recovery 
• Reduced need for general anesthesia and associated risks 
18.6.2. Potential Benefit Using the ACURATE Transfemoral Aortic Valve System 
Potential benefits that may be associated specifically with use of the ACURATE 
Transfemoral Aortic Valve System compared to other TAVR systems include the following. 
• Top-down implantation technique intended to compress the native calcified leaflet 
tissue below the upper crown, thus capturing the native leaflets in the waist of the 
device 
• A lower crown which protrudes minimally towards the LVOT, thus reducing the 
chance of conduction disturbances 

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• Low aortic gradients due to the supra-annular positioning of the deployed valve  
• Reduced incidence of paravalvular aortic regurgitation due to the sealing skirt  
• Delivery system with a flexible shaft facilitating easy tracking in tortuous anatomy and 
a controlled 2-step deployment process 
18.7. Risk to Benefit Rationale 
Review of the aforementioned clinical benefits versus risks takes into account the known 
risks/benefits that have been identified in the published literature on other TAVR devices. 
The estimation of risk also includes clinical experience with the ACURATE Transfemoral 
Aortic Valve System and earlier generations of the device. When used according to the 
DFU/IFU, all known risks associated with the TAVR procedure and the specific use of the 
ACURATE Transfemoral Aortic Valve System are mitigated to acceptable limits comparable 
to existing TAVR devices. Specific design features of the valve may improve TAVR 
procedural safety. These include top-down implantation to capture the native calcified 
leaflets in the waist of the device and a lower crown that protrudes minimally towards the 
LVOT and may minimize conduction disturbances. The supra-annular positioning may result 
in lower aortic pressure gradients. The sealing skirt may provide long term benefit as it is 
designed to minimize paravalvular regurgitation, which has been associated with long term 
mortality in TAVR. 
19. Safety Reporting 
19.1. Reportable Events by Investigational Center to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event that occurs in 
any of the following categories; reporting requirements are described below in Table 19.4-1. 
• All serious adverse events 
• All adverse events and adverse device effects (through 12 months) 
• All investigational device deficiencies  
• Unanticipated adverse device effects/unanticipated serious adverse device effects  
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 

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Any reportable event required by the protocol, experienced by the study subject after 
informed consent and once considered enrolled in the study, whether during or subsequent to 
the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation. Death should not be recorded as an AE but 
should only be reflected as an outcome of one (1) specific SAE (see Table 19.2-1 for AE 
definitions). 
In-patient hospitalization is defined as the subject being admitted to the hospital, with the 
following exceptions. 
• A hospitalization that is uncomplicated and elective/planned (i.e., planned prior to 
enrollment) does not have to be reported as an SAE. 
• If complications or AEs occur during an elective/planned (i.e., planned prior to 
enrollment) hospitalization after enrollment, the complications and AEs must be 
reported as AEs or SAEs if they meet the protocol-specified definitions. 
For the randomized cohort, event reporting (eCRF data entry) is required beginning from the 
time of randomization. For the Roll-In and ACURATE Prime XL Nested Registry cohorts, 
event reporting (eCRF data entry) is required beginning from the time an attempt is made to 
insert the ACURATE Transfemoral Aortic Valve System into the subject’s femoral artery. 
Refer to Section 18 for the known risks associated with the study devices (test and control). 
Based on the VARC66,67 recommendations and definitions, the adverse events and/or safety 
endpoints requiring adjudication by the CEC include the following. 
• Mortality: all-cause, cardiovascular, and non-cardiovascular  
• Stroke: disabling and non-disabling  
• Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and 
spontaneous (>72 hours post index procedure) 
• Bleeding events: life-threatening (or disabling) and major (through 5 years)  
• Acute kidney injury (≤7 days post index procedure): based on the AKIN System 69,70 
Stage 3 (including renal replacement therapy) or Stage 2  
• Vascular complications: major (including annular rupture; through 5 years) 
• Repeat procedure for valve-related dysfunction (surgical or interventional therapy)  
• Hospitalization for valve-related symptoms or worsening congestive heart failure 
(NYHA class III or IV) 
• New permanent pacemaker implantation resulting from new or worsened conduction 
disturbances 
• New onset of atrial fibrillation or atrial flutter  
• Coronary obstruction: periprocedural (≤72 hours post index procedure) 

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• Ventricular septal perforation: periprocedural (≤72 hours post index procedure) 
• Mitral apparatus damage: periprocedural (≤72 hours post index procedure) 
• Cardiac tamponade: periprocedural (≤72 hours post index procedure) 
• Prosthetic aortic valve malpositioning, including valve migration, valve embolization, 
or ectopic valve deployment 
• TAV-in-TAV deployment 
• Prosthetic aortic valve thrombosis 
• Prosthetic aortic valve endocarditis 
Details on the CEC events and procedures are outlined in the CEC charter.  Tests and images 
required to adjudicate these events are specified in the event definitions (see Table 25.2-1). 
19.2. Definitions and Classification 
Adverse event definitions are provided in Table 19.2-1. Administrative edits were made on 
the safety definitions from ISO 14155 and MEDDEV 2.7/3 for clarification purposes. 
Table 19.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
 
 
 
Any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or 
other persons, whether or not related to the investigational medical device.  
Note 1: This includes events related to the investigational medical device or 
comparator. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to 
the investigational medical device.  
Adverse Device Effect 
(ADE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational medical device 
Note 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, the 
installation, the operation, or any malfunction of the investigational medical 
device. 
Note 2: This definition includes any event resulting from use error or intentional 
abnormal use of the investigational medical device. 
Serious Adverse Event 
(SAE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Note 1: This definition meets the reporting objectives and requirements of ISO 
14155 and MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to serious deterioration in the health of the subject as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolongation of existing hospitalization, or 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
Note 2: Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without a serious deterioration in 
health, is not considered a serious adverse event.  
Serious Adverse 
Device Effect (SADE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
 
Unanticipated Adverse 
Device Effect (UADE) 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects.   
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current version of the risk analysis report. 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its 
nature, incidence, severity or outcome has been identified in the risk analysis 
report. 
Serious Health Threat 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an imminent 
risk of death or a serious deterioration in the health of subjects, users or other 
persons, and that requires prompt remedial action for other subjects, users or other 
persons. 
Note 1: This would include events that are of significant and unexpected nature 
such that they become alarming as a potential serious health hazard or possibility 
of multiple deaths occurring at short intervals. 
Device Deficiency 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
An inadequacy of an investigational medical device related to its identity, quality, 
durability, reliability, safety or performance. This may include malfunctions, use 
error, or inadequacy in the information supplied by the manufacturer. 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• Emergency room visit that does not result in in-patient admission  
Note 1: Although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria (e.g., 
medical or surgical intervention to prevent permanent impairment or 
damage) 
• Elective and pre-planned treatment/surgery for a pre-existing condition that 
is documented in the subject’s record at the time of consent/enrollment 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
• Admission for social reasons and/or respite care in the absence of any 
deterioration in the subject’s general condition (e.g., subject is homeless, 
caregiver relief) 
Pre-planned, protocol-specified admission related to the clinical study (e.g., 
procedure required by protocol) 
Prolongation of 
Hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note 1: New adverse events occurring during the hospitalization are evaluated to 
determine if they prolonged hospitalization or meet another SAE criterion. 
 
19.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the reportable AE/SAE to the study device 
and procedure. See criteria in Table 19.3-1:  
Table 19.3-1: Criteria for Assessing Relationship of Study Device and Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Ref: MEDDEV 2.7/3 
Relationship to the device or procedures can be excluded when: 
• the event is not a known side effect of the product category the device belongs 
to or of similar devices and procedures; 
• the event has no temporal relationship with the use of the investigational 
device or the procedures; 
• the serious event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically 
implausible; 
• the discontinuation of medical device application or the reduction of the level 
of activation/exposure - when clinically feasible – and reintroduction of its use 
(or increase of the level of activation/exposure), do not impact on the serious 
event; 
• the event involves a body-site or an organ not expected to be affected by the 
device or procedure; 
• the serious event can be attributed to another cause (e.g. an underlying or 
concurrent illness/ clinical condition, an effect of another device, drug, 
treatment or other risk factors); 
• the event does not depend on a false result given by the investigational device 
used for diagnosis, when applicable; harms to the subject are not clearly due to 
use error; 
In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 

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Table 19.3-1: Criteria for Assessing Relationship of Study Device and Procedure to 
Adverse Event 
Classification 
Description 
Unlikely Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases where relatedness cannot be assessed, or no information has been 
obtained should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device   seems relevant and/or 
the event cannot be reasonably explained by another cause, but additional 
information may be obtained. 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the investigational device or comparator or 
with procedures beyond reasonable doubt when: 
• the event is a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
• the event has a temporal relationship with investigational device 
use/application or procedures; 
• the event involves a body-site or organ that 
- the investigational device or procedures are applied to; 
- the investigational device or procedures have an effect on; 
• the serious event follows a known response pattern to the medical device (if 
the response pattern is previously known); 
• the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
• other possible causes (e.g. an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug or treatment) have been 
adequately ruled out; 
• harm to the subject is due to error in use; 
• the event depends on a false result given by the investigational device used for 
diagnosis, when applicable 
In order to establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious event. 
 
19.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 19.4-1. 

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Table 19.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline (premarket studies) 
(MEDDEV 2.7/3: CLINICAL 
INVESTIGATIONS: SERIOUS ADVERSE 
EVENT REPORTING UNDER DIRECTIVES 
90/385/EEC AND 93/42/EEC) 
Unanticipated Adverse 
Device Effect / 
Unanticipated Serious 
Adverse Device Effect  
(UADE/USADE) 
Complete AE eCRF page 
with all available new and 
updated information.  
 
• Within 1 business day of first becoming 
aware of the event. 
• Terminating at the end of the study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event.  
• At request of Sponsor.  
Serious Adverse Event  
(SAE) 
Complete AE eCRF page 
with all available new and 
updated information.  
• Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations.  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event. 
• At request of Sponsor 
Serious Adverse Device 
Effects 
(SADE) 
 
Complete AE eCRF page 
with all available new and 
updated information. 
• Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations.  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event.  
• When documentation is available 
• At Sponsor request.  
Device Deficiencies 
(including but not 
limited to failures, 
malfunctions, and 
product 
nonconformities) 
Note:  Any 
Investigational Device 
Complete AE eCRF page 
with all available new and 
updated information.  
Investigational Device: 
• Within 3 calendar days of first becoming 
aware of the event.  
• Reporting required through 12 months 
Control Device: 
• As required per DFU/IFU and as per 
local/regional regulations 

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Table 19.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline (premarket studies) 
(MEDDEV 2.7/3: CLINICAL 
INVESTIGATIONS: SERIOUS ADVERSE 
EVENT REPORTING UNDER DIRECTIVES 
90/385/EEC AND 93/42/EEC) 
Deficiency that might 
have led to a serious 
adverse event if a) 
suitable action had not 
been taken or b) 
intervention had not 
been made or c) if 
circumstances had been 
less fortunate is 
considered a reportable 
event. 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event. 
Investigational Device: 
• At request of Sponsor  
Adverse Event including 
Adverse Device Effects 
(AE/ADE) 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• In a timely manner (e.g., recommend within 
10 business days) after becoming aware of 
the information 
• Reporting required through 12 months 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event.  
• At request of Sponsor 
* Please note that pre-market studies are clinical studies with investigational devices or with medical devices 
that bear the regulatory approval and are not being used for the same approved indications. 
 
19.5. Device Deficiencies 
Complaint reporting of any device deficiencies for any commercially available products used 
should be carried out using the manufacturer’s processes.    
19.5.1. Boston Scientific Device Deficiencies 
All device deficiencies related to the test device or future iterations will be documented and 
reported to BSC. If possible, the device(s) should be returned to BSC for analysis. 
Instructions for returning the investigational device(s) will be provided in the study Manual 
of Operations. If it is not possible to return the device, the investigator should document why 
the device was not returned and the final disposition of the device. Device deficiencies 
should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency would be recorded as an adverse event on the appropriate eCRF. 

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19.5.2. Control Device Deficiencies 
Device deficiencies related to use of the control device should be reported per the DFU/IFU 
and per applicable local/regional requirements. If an AE results from a device deficiency or 
other device issue, the AE must be reported on the appropriate eCRF. 
19.6. Reporting to Regulatory Authorities / IRBs / REBs / HRECs / IECs / Investigators 
Boston Scientific Corporation will notify all participating study centers if UADEs, SAEs, 
SADEs, or investigational device deficiencies occur which imply a possible increase in the 
anticipated risk of the procedure or use of the device or if the occurrence of certain 
SAEs/SADEs requires changes to the protocol or the conduct of the study in order to further 
minimize the unanticipated risks. 
Boston Scientific Corporation is responsible for reporting adverse event information to all 
participating Principal Investigators, IRBs/REBs/HRECs/IECs, and regulatory authorities, as 
applicable.  
The Principal Investigator is responsible for informing the IRB/REB/HREC/IEC and 
regulatory authorities of UADEs and SAEs as required by local/regional regulations. 
20. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, the relevant parts of ISO 14155 and the ICH 
guidelines for GCP, any applicable national regulations, and local Ethics Committee and/or 
Regulatory authority, as applicable. The ICF must be accepted by BSC or its delegate (e.g., 
CRO) and approved by the center’s IRB/REB/HREC/IEC, or central IRB, if applicable. 
Boston Scientific Corporation will provide a study-specific template of the ICF to 
investigators participating in this study. The ICF template may be modified to meet the 
requirements of the investigative center’s IRB/REB/HREC/IEC. Any modification requires 
acceptance from BSC or authorized representative prior to use of the form. The ICF must be 
in a language understandable to the subject and if needed, BSC will assist the center in 
obtaining a written consent translation. Translated consent forms must also have IRB/REB/ 
HREC/IEC approval prior to their use. Privacy language shall be included in the body of the 
form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  

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• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions, if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout 
the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations, and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs the ICF, the subject shall be asked to provide 
informed consent for continued participation as soon as his/her medical condition allows. 
The original signed ICF will be retained by the center and a copy of the signed and dated 
document and any other written information must be given to the person signing the form.  
Note: Centers may use remote consent as allowed by institutional policy and the center’s 
IRB/REB/HREC/IEC. 
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., the United States Food and Drug 
Administration [FDA] requirement is within 5 working days of learning of such an event). 
Any violations of the informed consent process must be reported as deviations to the Sponsor 
and local regulatory authorities (e.g., IRB/REB/HREC/IEC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/REB/HREC/IEC. The new version of the ICF must be 
approved by the IRB/REB/HREC/IEC. Acceptance by Boston Scientific Corporation is 
required if changes to the revised ICF are requested by the center’s IRB/REB/HREC/IEC. 
The IRB/REB/HREC/IEC will determine the subject population to be re-consented. 
Study personnel should explain that even if a subject agrees to participate in the study and 
signs an ICF, the heart team and/or the CRC may determine that the subject is not a suitable 
candidate for the study and/or TAVR procedure. A confidential Screening/Enrollment Log 
will be maintained by the center to document select information about candidates who fail to 
meet the general or "other specific" entry criteria. 

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21. Committees 
21.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operations teams review safety 
data as they are reported by the centers throughout the duration of the study. During 
scheduled monitoring activities, clinical research monitors further support this review 
through their review of source documents and other data information. The BSC Medical 
Safety and Safety Trial Operations teams includes health care providers with expertise in 
cardiology and with the necessary therapeutic and subject matter expertise to evaluate and 
classify the events into the categories outlined above (Section 19). 
21.1.1. Clinical Events Committee 
A Clinical Events Committee (CEC) will be used in this study. A CEC is an independent 
group of individuals with pertinent expertise, including cardiovascular interventional therapy, 
cardiovascular surgery, and neurology, which reviews and adjudicates important endpoints 
and relevant adverse events reported by study investigators. The CEC will review a safety 
event dossier, which may include copies of subject source documents provided by study 
centers and adjudicate study endpoint related clinical events. The responsibilities, 
qualifications, membership, and committee procedures of the CEC are outlined in the CEC 
Charter.  
21.1.2. Data Monitoring Committee 
The DMC is responsible for the oversight review of all AEs. The DMC will include leading 
experts in cardiovascular interventional therapy, cardiovascular surgery, and biostatistics 
who are not participating in the study and who have no affiliation with BSC. During the 
course of the study, the DMC will review accumulating safety data to monitor the incidence 
of CEC events and other trends that would warrant modification or termination of the study. 
Responsibilities, qualifications, membership, and committee procedures are outlined in the 
DMC Charter. 
21.2. Case Review Committee 
A Case Review Committee (CRC) will be comprised of experienced cardiac surgeons and 
interventional cardiologists, including the Study Coordinating PIs, Center PIs, other 
Investigators, Proctors and Medical Consultants experienced in TAVR for their 
clinical/medical expertise, and the Sponsor for technical expertise on the ACURATE 
Transfemoral Aortic Valve System requirements. This committee will be responsible for the 
review of subject screening data to confirm eligibility given the increased surgical risk of the 
subject population being studied and to ensure consistency of subjects enrolled across study 
centers. Responsibilities, qualifications, membership, and committee procedures are outlined 
in the CRC Charter. Minutes are written for each CRC review session and the decisions are 
documented in these minutes and provided to the centers as appropriate. 

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21.3. Steering Committee 
A Steering Committee consisting of Sponsor Clinical Management, the Study Coordinating 
PIs, cardiac surgeons, and other investigators experienced in TAVR will be convened. 
Responsibilities may include oversight of the overall conduct of the study with regard to 
protocol development, study progress, subject safety, overall data quality and integrity, as 
well as disseminating any study results through appropriate scientific sessions and 
publications. Steering Committee members may participate in the review and approval of all 
requests for data analysis, abstract and manuscript preparation and submission.  
22. Suspension or Termination 
22.1. Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or business reasons and reasons related 
to protection of subjects. Investigators, associated IRBs/REBs, and regulatory authorities, as 
applicable, will be notified in writing in the event of study termination. 
22.1.1. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• Suspicion of an unacceptable risk. In this case, the sponsor shall suspend the clinical 
investigation while the risk is assessed. The sponsor shall terminate the clinical 
investigation if an unacceptable risk which cannot be controlled is confirmed. 
• Instructions by the IRB/REB/HREC/IEC or regulatory authorities to suspend or 
terminate the clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of 
the device. 
22.2. Termination of Study Participation by the Investigator or Withdrawal of IRB / REB 
/ HREC / IEC Approval 
Any investigator, or associated IRB/REB/HREC/IEC or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with suitable 
written notice to BSC. Investigators, associated IRBs/REBs/HRECs/IECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these occurrences. 

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22.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating centers by BSC. The IRB/REB/ 
HREC/IEC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/REB/HREC/IEC terminates participation in the study, participating 
investigators, associated IRBs/REBs/HRECs/IECs, and regulatory authorities, as applicable, 
will be notified in writing. Detailed information on how enrolled subjects will be managed 
thereafter will be provided by BSC. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility, detailed information on how enrolled 
subjects will be managed thereafter will be provided by BSC. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to BSC, unless this action would jeopardize the rights, safety, or 
welfare of the subjects. 
22.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific Corporation reserves the right to stop the inclusion of subjects at a study 
center at any time after the study initiation visit if no subjects have been enrolled for a period 
beyond 4 months after center initiation, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of center participation, all study devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB/REB/HREC/IEC and regulatory authorities, as 
applicable, will be notified. Study subjects will be contacted, as applicable, and be informed 
of changes to study visit schedule. 
23. Study Registration and Results 
23.1. Study Registration 
To comply with applicable laws and regulations, the study has been registered on the 
publicly accessible database ClinicalTrials.gov (NCT03735667). 
23.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IRB/REB/HREC/IEC and 
regulatory authorities, as applicable in accordance with the Boston Scientific Policy and local 

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requirements. As applicable an abbreviated Clinical Investigation Report will be made 
available on a publicly accessible database. 
23.3. Publication Policy 
Boston Scientific Corporation requires disclosure of its involvement as a sponsor or financial 
supporter in any publication or presentation relating to a BSC study or its results. Boston 
Scientific Corporation will submit study results for publication (regardless of study outcome) 
following the conclusion or termination of the study. Boston Scientific Corporation adheres 
to the Contributorship Criteria set forth in the Uniform Requirements of the International 
Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In order to ensure the 
public disclosure of study results in a timely manner, while maintaining an unbiased 
presentation of study outcomes, BSC personnel may assist authors and investigators in 
publication preparation provided the following guidelines are followed. 
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Steering Committee 
at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(http://www.bostonscientific.com/en-US/data-sharing-requests.html).  
24. Bibliography 
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79. Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. 
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80. Brouwer J, Nijenhuis VJ, Delewi R, et al. Aspirin with or without clopidogrel after 
transcatheter aortic-valve implantation. N Engl J Med 2020;383:1447-57. 
81. Nijenhuis VJ, Brouwer J, Delewi R, et al. Anticoagulation with or without clopidogrel 
after transcatheter aortic-valve implantation. N Engl J Med 2020;382:1696-707. 
82. Medtronic CoreValve System PMA P130021/S002: FDA Summary of Safety and 
Effectiveness Data. 
83. Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika 
1983;70:659-63. 
84. EAST® 6.5 Software, Cytel, Inc. 2018. 

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85. Webb J, Gerosa G, Lefèvre T, et al. Multicenter evaluation of a next-generation 
balloon-expandable transcatheter aortic valve. J Am Coll Cardiol 2014;64:2235-43. 
86. Makkar RR, Fontana G, Jilaihawi H, et al. Possible subclinical leaflet thrombosis in 
bioprosthetic aortic valves. N Engl J Med 2015;373:2015-24. 
87. Pache G, Schoechlin S, Blanke P, et al. Early hypo-attenuated leaflet thickening in 
balloon-expandable transcatheter aortic heart valves. Eur Heart J 2016;37:2263-71. 
88. Søndergaard L, De Backer O, Kofoed KF, et al. Natural history of subclinical leaflet 
thrombosis affecting motion in bioprosthetic aortic valves. Eur Heart J 2017;38:2201-7. 
89. Chakravarty T, Søndergaard L, Friedman J, et al. Subclinical leaflet thrombosis in 
surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet 
2017;389:2383-92. 
90. Hansson NC, Grove EL, Andersen HR, et al. Transcatheter aortic valve thrombosis: 
incidence, predisposing factors, and clinical implications. J Am Coll Cardiol 
2016;68:2059-69. 
91. Ruile P, Jander N, Blanke P, et al. Course of early subclinical leaflet thrombosis after 
transcatheter aortic valve implantation with or without oral anticoagulation. Clin Res 
Cardiol 2017;106:85-95. 
92. Jose J, Sulimov DS, El-Mawardy M, et al. Clinical bioprosthetic heart valve thrombosis 
after transcatheter aortic valve replacement: incidence, characteristics, and treatment 
outcomes. J Am Coll Cardiol Intv 2017;10:686-97. 
93. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for 
cardiovascular clinical trials: a consensus report from the Bleeding Academic Research 
Consortium. Circulation 2011;123:2736-47. 
94. Ndrepepa G, Schuster T, Hadamitzky M, et al. Validation of the Bleeding Academic 
Research Consortium definition of bleeding in patients with coronary artery disease 
undergoing percutaneous coronary intervention. Circulation 2012;125:1424-31. 
95. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: 
utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J 
Med 1994;96:200-9. 
96. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur 
Heart J 2007;28:2525-38. 
97. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update 
incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of 
cardiac rhythm abnormalities: a report of the American College of Cardiology 
Foundation/American Heart Association Task Force on Practice Guidelines and the 
Heart Rhythm Society. J Am Coll Cardiol 2013;61:e6-75. 
98. De Backer O, Dangas GD, Jilaihawi H, et al. Reduced leaflet motion after transcatheter 
aortic-valve replacement. N Engl J Med 2020;382:130-9. 

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99. Sharp AS, Michev I, Maisano F, et al. A new technique for vascular access 
management in transcatheter aortic valve implantation. Catheter Cardiovasc Interv 
2010;75:784-93. 
100. Généreux P, Kodali S, Leon MB, et al. Clinical outcomes using a new crossover 
balloon occlusion technique for percutaneous closure after transfemoral aortic valve 
implantation. J Am Coll Cardiol Intv 2011;4:861-7. 
25. Abbreviations and Definitions  
25.1. Abbreviations 
Abbreviations are shown in Table 25.1-1.   
 
 
Table 25.1-1: Abbreviations and Acronyms 
Abbreviation/Acronym 
Definition 
ADE 
adverse device effect 
AE 
adverse event 
AKIN 
Acute Kidney Injury Network 
AR 
aortic regurgitation 
AS 
aortic stenosis 
AV 
atrioventricular 
AVA 
aortic valve area 
AVR 
aortic valve replacement 
BARC 
Bleeding Academic Research Consortium 
BAV 
balloon aortic valvuloplasty 
BMI 
body mass index 
BSA 
body surface area 
BSC 
Boston Scientific Corporation 
CAD 
coronary artery disease 
CBC 
complete blood count 
CEC 
Clinical Events Committee 
CK 
creatine kinase 
CK-MB 
creatine kinase-myoglobin band, a fraction of creatine kinase 
CRC 
Case Review Committee 
CT 
computed tomography 
CVA 
cerebrovascular accident 
DFU 
Directions for Use 
DVI 
Doppler velocity index 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOA 
effective orifice area 
GCP 
Good Clinical Practices 

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Table 25.1-1: Abbreviations and Acronyms 
Abbreviation/Acronym 
Definition 
GDPR 
General Data Protection Regulation 
HCP 
healthcare personnel 
HREC 
Human Research Ethics Committee 
IB 
Investigator Brochure  
ICF 
Informed Consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
iEOA 
indexed effective orifice area 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISO 
International Organization for Standardization 
ITT 
intention-to-treat 
LBBB 
left bundle branch block 
LV 
left ventricle 
LVEF 
left ventricular ejection fraction 
MACCE 
major adverse cardiovascular and cerebrovascular events 
MI 
myocardial infarction 
MRI 
magnetic resonance imaging 
mRS 
Modified Rankin Scale 
NIHSS 
National Institutes of Health Stroke Scale 
NYHA 
New York Heart Association  
OAC 
oral anticoagulant 
PG 
performance goal 
PPM 
permanent pacemaker 
QOL 
quality of life 
REB 
Research Ethics Board 
RLM 
reduced leaflet motion 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAVR 
surgical aortic valve replacement 
TAVI/TAVR 
transcatheter aortic valve implantation/replacement 
TEE 
transesophageal Doppler echocardiography 
TIA 
transient ischemic attack 
TTE 
transthoracic Doppler echocardiography 
UADE 
unanticipated adverse device effect 
URL 
upper reference limit (defined as 99th percentile of normal reference range) 
VARC 
Valve Academic Research Consortium 
 

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25.2. Definitions 
Terms are defined in Table 25.2-1. See Table 25.1-1 for abbreviations. 
Table 25.2-1: Definitions 
Term 
Definition 
ACUTE KIDNEY 
INJURY (AKI) 
(AKIN System69,70) 
Change in serum creatinine (up to 7 days) compared to baseline: 
• Stage 1: Increase in serum creatinine to 150–199% (1.5–1.99 × increase 
compared with baseline) OR increase of ≥0.3 mg/dl (≥26.4 mmol/L)  
• Stage 2: Increase in serum creatinine to 200–299% (2.0–2.99 × increase 
compared with baseline) 
• Stage 3: Increase in serum creatinine to ≥300% (>3 × increase compared with 
baseline) OR serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute 
increase of at least 0.5 mg/dL (44 mmol/L) 
-OR-  
Based on urine output (up to 7 days): 
• Stage 1: <0.5 ml/kg per hour for >6 but <12 hours 
• Stage 2: <0.5 ml/kg per hour for >12 but <24 hours 
• Stage 3: <0.3 ml/kg per hour for ≥24 hours or anuria for ≥12 hours 
Note: Subjects receiving renal replacement therapy are considered to meet Stage 
3 criteria irrespective of other criteria. 
ACUTE VESSEL 
OCCLUSION 
The state of complete luminal obstruction with no antegrade blood flow 
ADVERSE EVENT 
(AE)  
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
Any untoward medical occurrence, unintended disease or injury or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. 
Note: This definition includes events related to the investigational medical device 
or the comparator. 
Note: This definition includes events related to the procedures involved. 
Note: For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
ADVERSE EVENT 
BECOME AWARE 
DATE 
The become aware date for an adverse event that requires reporting per the 
protocol is the date that study personnel listed on the Delegation of Authority Log 
identify or are notified of the event. 
ADVERSE DEVICE 
EFFECT (ADE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
Adverse event related to the use of an investigational medical device 
Note: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device.  
Note: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
AORTIC DISSECTION 
Intimal tear resulting in blood splitting the aortic media and producing a false 
lumen that can progress in an antegrade or retrograde direction Aortic dissection 
is further classified using Stanford classification (Types A and B depending on 
whether ascending or descending aorta involved) or DeBakey classification 
(Types I, II and III) [see Figure below]. 

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Table 25.2-1: Definitions 
Term 
Definition 
 
AORTIC 
REGURGITATION 
(AR) 
The leaking of the aortic valve that causes blood to flow in the reverse direction 
during ventricular diastole, from the aorta into the left ventricle. 
The echocardiographic findings in severe aortic regurgitation include the 
following. 
• An AR color jet dimension >60% of the left ventricular outflow tract diameter 
(may not be true if the jet is eccentric)  
• The pressure half-time of the regurgitant jet is <250 msec  
• Early termination of the mitral inflow (due to increase in LV pressure due to 
the AR)  
• Early diastolic flow reversal in the descending aorta.  
 
• Regurgitant volume >60 mL  
• Regurgitant fraction >55% 
ARRHYTHMIA 
Any variation from the normal rhythm of the heartbeat, including sinus 
arrhythmia, premature beat, heart block, atrial fibrillation, atrial flutter and 
tachycardia. Complete heart block, ventricular tachycardia and ventricular 
fibrillation are considered major arrhythmias. Data should be collected on any 
new arrhythmia resulting in hemodynamic instability or requiring therapy 
(therapy includes electrical/medical cardioversion or initiation of a new 
medication [oral anticoagulation, rhythm or rate controlling therapy]).  
New onset atrial fibrillation or atrial flutter (AF) is diagnosed as any arrhythmia 
within hospitalization that has the ECG characteristics of AF and lasts 
sufficiently long to be recorded on a 12-lead ECG, or at least 30 seconds on a 
rhythm strip.  
The therapeutic approach to new-onset AF (spontaneous conversion, electrical or 
medical cardioversion, initiation of oral anticoagulation, and rate or rhythm 
control medications) and any clinical consequences should be documented.   
Note: See also definitions for conductance disturbance and permanent 
pacemaker. 
BLEEDING66,67   
Life-threatening or Disabling Bleeding 
• Fatal bleeding (Bleeding Academic Research Consortium [BARC] type 593,94) 
• Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or 
pericardial necessitating pericardiocentesis, or intramuscular with 
compartment syndrome (BARC type 3b and 3c)  

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Table 25.2-1: Definitions 
Term 
Definition 
• Bleeding causing hypovolemic shock or severe hypotension requiring 
vasopressors or surgery (BARC type 3b)  
• Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood 
or packed red blood cells (RBC) transfusion ≥4 units (BARC type 3b)* 
Major Bleeding (BARC type 3a) 
• Overt bleeding either associated with a drop in the hemoglobin level of at least 
3.0g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or 
causing hospitalization or permanent injury, or requiring surgery AND does 
not meet criteria of life-threatening or disabling bleeding  
Minor Bleeding (BARC type 2 or 3a, depending on the severity) 
• Any bleeding worthy of clinical mention (e.g., access site hematoma) that does 
not qualify as life-threatening, disabling, or major 
* Given one unit of packed RBC typically will raise blood hemoglobin 
concentration by 1 g/dL, an estimated decrease in hemoglobin will be calculated. 
CARDIAC 
DECOMPENSATION 
Inability of the heart to maintain adequate circulation 
CARDIAC 
TAMPONADE 
Evidence of a new pericardial effusion associated with hemodynamic instability 
and clearly related to the TAVR procedure. Clinical syndrome caused by the 
accumulation of fluid in the pericardial space, resulting in reduced ventricular 
filling and subsequent hemodynamic compromise. 
CARDIOGENIC 
SHOCK 
An insufficient forward cardiac output to maintain adequate perfusion of vital 
organs to meet ongoing demands for oxygenation and metabolism. Cardiogenic 
shock is due to either inadequate left ventricular pump function (such as in 
congestive heart failure) or inadequate left ventricular filling (such as in cardiac 
tamponade). Cardiogenic shock is defined as sustained hypotension (>30 
minutes) with evidence of tissue hypoperfusion including oliguria (<30 mL/h), 
cool extremities, cyanosis, and altered mental status. 
CEREBRAL 
INFARCTION 
Evidence of brain cell death from imaging studies or pathological examination. If 
there are clinical symptoms, then it is a stroke; otherwise, it is an asymptomatic 
cerebral infarction.  
CHRONIC RENAL 
INSUFFICIENCY 
Subject has chronic impairment of kidney function. 
CLINICAL 
PROCEDURAL 
SUCCESS  
(IN-HOSPITAL) 
Implantation of the device in the absence of death, disabling stroke, major 
vascular complications, and life-threatening or major bleeding 
CONDUCTION 
DISTURBANCES66,67  
Implant-related new or worsened cardiac conduction disturbances include 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 (RBBB), RBBB, intraventricular conduction delay, left bundle branch 
block (LBBB), left anterior fascicular block, or left posterior fascicular block, 
including block requiring permanent pacemaker implant 
Note: High grade AV block is considered persistent if it is present every time the 
underlying rhythm is checked. 
Note: See also definitions for arrhythmia and permanent pacemaker. 
CONVERSION TO 
OPEN SURGERY 
Conversion to open sternotomy during the TAVR procedure secondary to any 
procedure-related complications 

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Table 25.2-1: Definitions 
Term 
Definition 
CORONARY 
OBSTRUCTION 
 
Angiographic or echocardiographic evidence of a new, partial or complete, 
obstruction of a coronary ostium, either by the valve prosthesis itself, the native 
leaflets, calcifications, or dissection, occurring during or after the TAVR 
procedure. 
 
Mechanical coronary artery obstruction following TAVR or surgical AVR that 
typically occurs during the index procedure. Possible mechanisms for mechanical 
coronary obstruction include the following.  
• Impingement of the coronary ostia by the valve support structure in the setting 
of suboptimal valve positioning and/or ‘small aortic root’ anatomy  
• Embolization from calcium, thrombus, air, or endocarditis displacement of 
native aortic valve leaflets towards the coronary ostia during TAVR  
• Suture-related kinking or obstruction or cannulation related obstruction of the 
coronary ostia associated with surgical AVR 
The diagnosis of TAVR-associated coronary obstruction can be determined by 
imaging studies (coronary angiography, intravascular ultrasound, multi-slice CT 
angiography, or echocardiography), surgical exploration, or autopsy findings. 
Cardiac biomarker elevations and ECG changes indicating new ischemia provide 
corroborative evidence. 
DATA CATEGORIES 
Data categories as defined by GDPR are listed below. 
Personal Data: 
GDPR defines “Personal Data” to be any information relating to an identified or 
identifiable natural person (‘data subject’); an identifiable natural person is one 
who can be identified, directly or indirectly, in particular by reference to an 
identifier such as a name, an identification number, location data, an online 
identifier or to one or more factors specific to the physical, physiological, genetic, 
mental, economic, cultural or social identity of that natural person. 
Sensitive Personal Data: 
GDPR defines “Sensitive Personal Data” as a subset of Personal Data, which, due 
to their nature have been classified as deserving additional privacy and security 
protections because their processing may create a risk for an individual’s 
fundamental right and freedom. This subset includes but is not limited to the 
following: racial, ethnic origin or ethnicity; political opinions; religious or 
philosophical beliefs; trade union membership; genetic data; biometric data for 
the purpose of uniquely identifying a natural person; health data (including 
gender, family medical history, etc.); sex life or sexual orientation; criminal 
records or allegations of crimes (requires an even higher standard of protection). 
Identifiers: 
“Identifiers” are Personal Data that can be used alone or in combination with 
other identifiers to identify an individual. Identifiers include but are not limited to 
the following:  
• All government-issued identification numbers (including but not limited to 
names, social security number, certificate/license numbers, passport, national 
ID) 
• All financial account numbers (including but not limited to bank account 
numbers, payment numbers, bank or credit card numbers)  
• All geographic subdivisions smaller than a state, including street address, 
city, county, precinct, ZIP code, and their equivalent geocodes, except for the 

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Table 25.2-1: Definitions 
Term 
Definition 
initial three digits of the ZIP code if, according to the current publicly 
available data from the Bureau of the Census, the geographic unit formed by 
combining all ZIP codes with the same three initial digits contains more than 
20,000 people and/or the initial three digits of a ZIP code for all such 
geographic units containing 20,000 or fewer people is changed to 000 
• All elements of dates (except year) for dates that are directly related to an 
individual, including birth date, admission date, discharge date, death date, 
and all ages over 89 and all elements of dates (including year) indicative of 
such age, except that such ages and elements may be aggregated into a single 
category of age 90 or older 
• Telephone numbers 
• Fax numbers 
• Device identifiers and serial numbers 
• E-mail addresses 
• Web Universal Resource Locators (URLs) 
• Internet Protocol (IP) addresses 
• Medical record numbers 
• Biometric identifiers, including finger and voice prints 
• Health plan beneficiary numbers 
• Full-face photographs and any comparable images 
Any other unique identifying number, characteristic, or code (including subject 
ID number) 
DEATH  
 
All-cause Death 
Death from any cause after a valve intervention. 
Cardiovascular Death 
Any one of the following criteria is met. 
• Any death due to proximate cardiac cause (e.g., myocardial infarction, cardiac 
tamponade, worsening heart failure) 
• Sudden or unwitnessed death  
• Death of unknown cause 
• Death caused by noncoronary vascular conditions such as neurological events, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other 
vascular disease  
• All procedure-related deaths, including those related to a complication of the 
procedure or treatment for a complication of the procedure  
• All valve-related deaths including structural or nonstructural valve dysfunction 
or other valve-related adverse events  
Non-cardiovascular Death 
• Any death in which the primary cause of death is clearly related to another 
condition (e.g. trauma, cancer, suicide) 
DEVICE DEFICIENCY 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Any inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance.  
Note: Device deficiencies may include malfunctions, use errors, or inadequacy in 
the information supplied by the manufacturer. 
DEVICE FAILURE 
A device failure is identified whenever the criteria for device success are not met.  

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Table 25.2-1: Definitions 
Term 
Definition 
DEVICE MIGRATION 
Device migration is defined as an upward or downward displacement of the 
implanted valve from its original implant location, after initial correct positioning 
within the aortic annulus from its initial position, with or without consequences. 
This can be confirmed by X-ray, echocardiography, CT scan or MRI or valve 
migration demonstrated by direct assessment during open heart surgery or at 
autopsy. 
DEVICE RELATED 
COMPLICATIONS 
Complications associated with the device as it relates to delivery, placement, 
efficacy or durability; these may involve the implanted device or the delivery 
system.   
DEVICE SUCCESS 
(VARC 2 definition)67 
Absence of procedural mortality, correct positioning of a single valve into the 
proper anatomical location and intended performance of the study device 
(indexed effective orifice area [iEOA] >0.85 cm2/m2 for BMI <30 kg/m2 and 
iEOA >0.70 cm2/m2 for BMI ≥30 kg/m2 plus either a mean aortic valve gradient 
<20 mmHg or a peak velocity <3m/sec, and no moderate or severe prosthetic 
valve aortic regurgitation). 
ECTOPIC VALVE 
DEPLOYMENT 
Permanent deployment of the valve prosthesis in a location other than the aortic 
root. 
EMBOLISM 
Examples include a free flowing blood clot or lesion material that is located in the 
systemic or pulmonary circulation. Embolism may be manifested by a 
neurological event or a noncerebral embolic event. 
ENCEPHALOPATHY 
Altered mental state (e.g., seizures, delirium, confusion, hallucinations, dementia, 
coma, psychiatric episode, etc.) 
ENDOCARDITIS 
 
Infective endocarditis is diagnosed based on Duke criteria95 and necessitates the 
following.  
• Two major criteria -OR- 
• One major and three minor criteria -OR- 
• Five minor criteria 
Major Criteria 
• Positive blood culture for infective endocarditis  
o Typical microorganism consistent with infective endocarditis from 2 
separate blood cultures, as noted below. 
 Viridans streptococci, Streptococcus bovis, or HACEK group 
(Haemophilus [Haemophilus parainfluenzae, Haemophilus aphrophilus, 
and Haemophilus paraphrophilus], Actinobacillus 
actinomycetemcomitans [Aggregatibacter actinomycetemcomitans], 
Cardiobacterium hominis, Eikenella corrodens, Kingella kingae -OR-  
 Community-acquired Staphylococcus aureus or enterococci, in the 
absence of a primary focus  
 
-OR-  
o Microorganisms consistent with infective endocarditis from persistently 
positive blood cultures defined as noted below. 
 Two (2) positive cultures of blood samples drawn >12 hours apart -OR-   
 All of 3 or a majority of 4 separate cultures of blood (with first and last 
sample drawn 1 hour apart)  
• Evidence of endocardial involvement 
o Positive echocardiogram for infective endocarditis defined as noted below. 

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Table 25.2-1: Definitions 
Term 
Definition 
 Oscillating intracardiac mass on valve or supporting structures, in the 
path of regurgitant jets, or on implanted material in the absence of an 
alternative anatomic explanation -OR-   
 Abscess -OR-   
 New partial dehiscence of prosthetic valve  
 
-OR-  
o New valvular regurgitation (worsening or changing of preexisting murmur 
not sufficient) 
Minor Criteria 
• Predisposition: predisposing heart condition or intravenous drug use 
• Fever: temperature >38.0° C (100.4° F) 
• Vascular phenomena: major arterial emboli, septic pulmonary infarcts, 
mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and 
Janeway lesions 
• Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and 
rheumatoid factor 
• Microbiological evidence: positive blood culture but does not meet a major 
criterion as noted above or serological evidence of active infection with 
organism consistent with infective endocarditis 
• Echocardiographic findings: consistent with infective endocarditis but do not 
meet a major criterion as noted above  
Implanted valve endocarditis includes any infection involving an implanted 
valve. The diagnosis of operated valvular endocarditis is based on one of the 
following criteria.  
• Fulfillment of the Duke endocarditis criteria as defined above 
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as 
secondary to infection by histological or bacteriologic studies during a re-
operation 
• Findings of abscess, pus, or vegetation involving a repaired or replaced valve 
during an autopsy. 
EXPLANT 
Removal of the investigational valve implant for any reason. 
FRAILTY 
Slowness, weakness, exhaustion, wasting and malnutrition, poor endurance and 
inactivity, loss of independence.  
GENERAL DATA 
PROTECTION 
REGULATION 
The General Data Protection Regulation (GDPR) is a legal framework that sets 
guidelines for the collection and processing of personal information of 
individuals within the European Union. 
HEMOLYSIS 
 
Two plasma free hemoglobin values >40 mg/dL with the two readings taken 
within a single 48-hour period. If the second plasma free hemoglobin assessment 
is not performed within 48 hours following an initial determination of >40 
mg/dL, this would qualify as an AE. 
HOSTILE CHEST 
Any of the following or other reasons that make redo operation through 
sternotomy or right anterior thoracotomy prohibitively hazardous: 
• Abnormal chest wall anatomy due to severe kyphoscoliosis or other skeletal 
abnormalities (including thoracoplasty, Potts’ disease) 
• Complications from prior surgery 
• Evidence of severe radiation damage (e.g. skin burns, bone destruction, 
muscle loss, lung fibrosis or esophageal stricture) 

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Table 25.2-1: Definitions 
Term 
Definition 
• History of multiple recurrent pleural effusions causing internal adhesions 
HYPO-ATTENUATED 
LEAFLET 
THICKENING 
(HALT)73 
Hypo-attenuated leaflet thickening (HALT) is defined as visually identifiable 
increased leaflet thickness on contrast-enhanced multi-planar reformats, carefully 
aligned with the long and short axis of the valve prosthesis. The extent of HALT 
is classified as follows: 
 
The dashed yellow line indicates the orientation of the long axis views in the 
lower row, aligned with the center of the cusps. The extent of leaflet thickening 
can be graded on a subjective 4-tier grading scale along the curvilinear 
orientation of the leaflet. Typically, hypo-attenuated leaflet thickening appears 
meniscal-shaped on long axis reformats, with greater thickness at the base than 
towards the center of the leaflet. 
IMPLANTED 
ANALYSIS SET 
This population includes all subjects who sign an Informed Consent Form, are 
enrolled in the trial, and are implanted with the assigned, randomized study 
device. 
Note: If a subject receives 2 valves, the subject is assigned to the group 
corresponding to the first valve received.    
INTENT TO TREAT 
(ITT) ANALYSIS SET 
This population includes all subjects who sign an Informed Consent Form, are 
enrolled in the trial, and are randomized, whether or not an assigned study device 
is implanted. Subjects in the ITT population will be followed with their ITT 
cohort.  
Note: If a subject receives 2 valves, the subject is assigned to the group 
corresponding to the first valve received.    
INTERNAL 
MAMMARY ARTERY 
OR OTHER CRITICAL 
CONDUIT(S) 
CROSSING MIDLINE 
AND/OR ADHERENT 
TO POSTERIOR 
TABLE OF STERNUM 
A patent IMA graft that is adherent to the sternum such that injuring it during 
reoperation is likely. A patient may be considered extreme risk if any of the 
following are present:  
• The conduit(s) are radiographically indistinguishable from the posterior table 
of the sternum.  
• The conduit(s) are radiographically distinguishable from the posterior table of 
the sternum but lie within 2-3mm of the posterior table.  
INTRACRANIAL 
HEMORRHAGE 
Collection of blood between the brain and skull; subcategorized as epidural, 
subdural, and subarachnoid bleeds. 

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Table 25.2-1: Definitions 
Term 
Definition 
LEFT BUNDLE 
BRANCH BLOCK 
(LBBB) 
The appearance of typical complete LBBB in the three KEY leads (I, V1, and 
V6) with the following diagnostic criteria [see Figure below].  
• The heart rhythm must be supraventricular in origin  
• QRS widening to at least 0.12 sec  
• An upright (monophasic) QRS complex in leads I and V6; the QRS may be 
notched, but there should not be any q wave in either lead I or lead V6. 
• A predominantly negative QRS complex in lead V1; there may or may not be 
an initial small r wave in lead V1, that is, lead V1 may show either a QS or RS 
complex. 
 
 
 
 
 
 
 
 
 
 
LIVER DISEASE 
(SEVERE) 
/CIRRHOSIS 
Any of the following: 
• Child-Pugh class C  
• MELD score ≥10 
• Portal-caval, spleno-renal, or transjugular intrahepatic portal shunt  
• Biopsy proven cirrhosis with portal hypertension or hepatocellular dysfunction 
MITRAL VALVE 
APPARATUS 
DAMAGE 
Angiographic or echocardiographic evidence of a new damage to the mitral valve 
apparatus (chordae papillary muscle, or leaflet) during or after the TAVR 
procedure. 
MYOCARDIAL 
INFARCTION (MI) 
 
Periprocedural MI (≤72 hours after the index procedure) 
• New ischemic symptoms (e.g., chest pain or shortness of breath) or new 
ischemic signs (e.g., ventricular arrhythmias, new or worsening heart failure, 
new ST-segment changes, hemodynamic instability, new pathological Q waves 
in at least two contiguous leads, or imaging evidence of new loss of viable 
myocardium or new wall motion abnormality)  
 
-AND- 
• Elevated cardiac biomarkers (preferably CK-MB) within 72 h after the index 
procedure, consisting of at least one sample post-procedure with a peak value 
exceeding 15× upper reference limit (troponin) or 5× for CK-MB. If cardiac 
biomarkers are increased at baseline (>99th percentile), a further increase of at 
least 50% post-procedure is required AND the peak value must exceed the 
previously stated limit. 
Spontaneous MI (>72 hours after the index procedure) 
Any one of the following criteria applies. 
• Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at 
least one value above the 99th percentile URL, together with evidence of 
myocardial ischemia with at least one of the following 
o Symptoms of ischemia 

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Table 25.2-1: Definitions 
Term 
Definition 
o ECG changes indicative of new ischemia [new ST-T changes or new 
LBBB] 
o New pathological Q waves in at least two contiguous leads 
o Imaging evidence of new loss of viable myocardium or new wall motion 
abnormality 
• Sudden, unexpected cardiac death, involving cardiac arrest, often with 
symptoms suggestive of myocardial ischemia, and accompanied by 
presumably new ST-segment elevation, or new LBBB, and/or evidence of 
fresh thrombus by coronary angiography and/ or at autopsy, but death 
occurring before blood samples could be obtained, or at a time before the 
appearance of cardiac biomarkers in the blood. 
• Pathological findings of an acute myocardial infarction96. 
NEUROLOGICAL 
EVENT  
Any central, new neurological deficit, whether temporary or permanent and 
whether focal or global, that occurs after the subject emerges from anesthesia 
NEW YORK HEART 
ASSOCIATION 
CLASSIFICATION 
(NYHA) 
Classification system for defining cardiac disease and related functional 
limitations into four broad categorizations: 
Class I 
Subject with cardiac disease but without resulting limitations of 
physical activity. Ordinary physical activity does not cause 
undue fatigue, palpitation, dyspnea, or anginal pain. 
Class II 
Subjects with cardiac disease resulting in slight limitation of 
physical activity. They are comfortable at rest. Ordinary physical 
activity results in fatigue, palpitation, dyspnea, or anginal pain. 
Class III 
Subjects with cardiac disease resulting in marked limitation of 
physical activity. They are comfortable at rest. Less than 
ordinary physical activity causes fatigue, palpitation, dyspnea, or 
anginal pain. 
Class IV 
Subjects with cardiac disease resulting in inability to carry on 
any physical activity without discomfort. Symptoms of cardiac 
insufficiency or of the anginal syndrome may be present even at 
rest. If any physical activity is undertaken, discomfort is 
increased. 
 
NONSTRUCTURAL 
DYSFUNCTION 
 
Any abnormality not intrinsic to the valve itself that results in stenosis or 
regurgitation of the operated valve or hemolysis. The term nonstructural 
dysfunction refers to problems (exclusive of thrombosis and infection) that do not 
directly involve valve components yet result in dysfunction of an operated valve, 
as diagnosed by re-operation, autopsy, or clinical investigation. Nonstructural 
dysfunction includes the following. 
• Entrapment by pannus, tissue, or suture 
• Paravalvular leak 
• Inappropriate sizing or positioning 
• Residual leak or obstruction after valve implantation or repair 
• Clinically important intravascular hemolytic anemia 
• Development of aortic or pulmonic regurgitation as a result of technical errors 
• Dilatation of the sinotubular junction 
• Dilatation of the valve annulus after either valve replacement with stentless 
prostheses, new onset of coronary ischemia from coronary ostial obstruction, 
or paravalvular aortic regurgitation  

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Table 25.2-1: Definitions 
Term 
Definition 
OPERATIVE RISK67 
Operative risk is determined by a center cardiac surgeon and must be confirmed 
by the Case Review Committee (including a cardiac surgeon).  
Low: Estimated 30-day risk of mortality is < 3% 
Intermediate: Estimated 30-day risk of mortality is 3–10% 
High: Estimated 30-day risk of mortality is >10–15% 
Very High: Estimated 30-day risk of mortality is >15% 
Extreme: Estimated 30-day risk of irreversible morbidity or mortality is ≥50%   
PARAVALVULAR 
REGURGITATION  
 
Leakage due to a separation of the prosthetic valve from the annulus. Any 
evidence of leakage of blood around the device. Diagnosis of paravalvular 
regurgitation may be obtained from TEE/TTE, however, definitive diagnosis is 
obtained at re-operation, explant, or autopsy.  
PERMANENT 
PACEMAKER (PPM) 
IMPLANTATION97  
Implantation of new PPM after the index procedure resulting from new or 
worsened conduction disturbances  
• Procedure-related: PPM is implanted in subjects with new onset or worsened 
conduction disturbances occurring post index procedure 
• Not related to procedure: PPM is implanted in subjects with known 
conduction disturbances that did not advance after the index procedure. 
Note: See also definitions for arrhythmia and conductance disturbance. 
PORCELAIN AORTA 
Heavy circumferential calcification of the entire ascending aorta extending to the 
arch such that aortic cross-clamping is not feasible 
PROCEDURE 
RELATED 
COMPLICATIONS 
Complications associated with any part of the vascular access procedure, 
associated treatments or necessary secondary interventions that do not necessarily 
involve the device.  This includes morbidity associated with either pre-
medication, or anesthesia, or other adjunct to the surgical procedure.  Other 
technical errors including inappropriate subject selection, inappropriate operator 
techniques, measurements, or judgment that do not involve the device itself are 
also included.   
PROCEDURE-
RELATED EVENTS 
Events occurring during or as a direct result of the index procedure.  
REDUCED LEAFLET 
MOBILITY/MOTION 
(RLM)98 
Systolic leaflet excursion/motion is classified as: 
• Grade 0: normal/unrestricted;  
• Grade 1: partially restricted – limited to base;  
• Grade 2: mildly restricted – involving more than the base, but less than 50% 
of the leaflet along curvilinear dimensions;  
• Grade 3: moderately restricted – involving more than 50% but less than 
75% of the leaflet along curvilinear dimensions;  
• Grade 4: largely immobile. Quantitative assessment of leaflet motion is 
performed with a blood pool inversion volume rendered cine reconstruction 
throughout the cardiac cycle evaluating the bioprosthetic leaflets. 
REPEAT PROCEDURE 
FOR VALVE-
RELATED 
DYSFUNCTION 
Any surgical or percutaneous interventional catheter procedure that repairs, 
otherwise alters or adjusts, or replaces a previously implanted valve. In addition 
to surgical re-operations, balloon dilatation, interventional manipulation, 
repositioning, or retrieval, and other catheter-based interventions for valve-related 
complications are also considered re-interventions. Cardiac re-interventions will 
be categorized as repeat TAVR, valvuloplasty, or surgical AVR. 

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Table 25.2-1: Definitions 
Term 
Definition 
RESPIRATORY 
INSUFFICIENCY 
Inadequate ventilation or oxygenation 
RESPIRATORY 
FAILURE 
The need for ventilatory support for >72 hours associated with an inability to 
wean from the respirator for any reason. 
RIGHT 
VENTRICULAR 
INSUFFICIENCY 
• Defined as sequelae of right ventricular failure including the following. 
o Significantly decreased right ventricular systolic and/or diastolic function 
o Tricuspid valvular regurgitation secondary to elevated pressure 
• Clinical symptoms to include the following. 
o Hepatic congestion 
o Ascites 
o Anasarca 
o Presence of “hepato-jugular reflux” 
o Edema 
Severe right ventricular dysfunction or severe pulmonary hypertension is primary 
or secondary pulmonary hypertension with PA systolic pressures greater than 2/3 
of systemic pressure.  
SAFETY ANALYSIS 
SET 
This population includes all subjects in the ITT analysis set who have a study 
device implanted, regardless of the assigned treatment group. 
SERIOUS ADVERSE 
EVENT (SAE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
 
Adverse event that:  
• Led to a death 
• Led to serious deterioration in the health of the subject, that either resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient hospitalization or prolongation of existing hospitalization, or 
o medical or surgical intervention to prevent life- threatening illness  
• Led to fetal distress, fetal death or a congenital abnormality or birth defect 
Note: Planned hospitalization for a pre-existing condition, or a procedure 
required by the protocol, without serious deterioration in health, is not considered 
a serious adverse event. 
SERIOUS ADVERSE 
DEVICE EFFECT 
(SADE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event 
SOURCE DATA 
(per ISO 14155) 
All information in original records of clinical findings, observations, or other 
activities in a clinical investigation, necessary for the reconstruction and 
evaluation of the clinical investigation 
SOURCE DOCUMENT 
(per ISO 14155) 
Printed, optical or electronic document containing source data. Examples: 
hospital records, laboratory notes, device accountability records, photograhic 
negatives, radiographs, records kept at the investigation center, at the laboratories 
and at the medico-technical departments involvced in the clinical investigation.  
Note: If thermal paper from a device programmer is to be used for source 
documentation, signed and dated photocopies or printed portable document 
format files should be used instead or the strips should be electronically saved. 

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Table 25.2-1: Definitions 
Term 
Definition 
STROKE66,67  
 
Stroke is defined as an acute episode of focal or global neurological dysfunction 
caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage 
or infarction.  
Stroke Classification 
• Ischemic Stroke is defined as an acute episode of focal cerebral, spinal, or 
retinal dysfunction caused by an infarction of central nervous system tissue.  
• Hemorrhagic Stroke is defined as an acute episode of focal or global cerebral 
or spinal dysfunction caused by an intraparenchymal, intraventricular, or 
subarachnoid hemorrhage 
Note: The CEC will adjudicate ischemic versus hemorrhagic stroke. 
Note: A stroke may be classified as undetermined if there is insufficient 
information to allow categorization as ischemic or hemorrhagic 
Stroke Diagnostic Criteria  
• Rapid onset of a focal or global neurological deficit with at least one of the 
following: change in level of consciousness, hemiplegia, hemiparesis, 
numbness or sensory loss affecting one side of the body, dysphasia or aphasia, 
hemianopia, amaurosis fugax, or other neurological signs or symptoms 
consistent with stroke 
• Duration of a focal or global neurological deficit ≥24 h; OR <24 h, if available 
neuroimaging documents a new hemorrhage or infarct; OR the neurological 
deficit results in death 
• No other readily identifiable nonstroke cause for the clinical presentation (e.g., 
brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacological influences), to be determined by or in conjunction with 
designated neurologist 
• Confirmation of the diagnosis by at least one of the following.  
o Neurology or neurosurgical specialist  
o Neuroimaging procedure (MRI or CT scan), but stroke may be diagnosed on 
clinical grounds alone 
Note: Subjects with non-focal global encephalopathy will not be reported as a 
stroke without unequivocal evidence based upon neuroimaging studies (CT scan 
or brain MRI).  
Stroke Definitions 
Diagnosis as above, preferably with positive neuroimaging study 
• Non-disabling: Modified Rankin Scale (mRS) score <2 at 90 days OR one that 
does not result in an increase of at least one mRS category from an 
individual’s pre-stroke baseline 
• Disabling: Modified Rankin Scale score ≥2 at 90 days AND an increase of at 
least one mRS category from an individual’s pre-stroke baseline  
Note: Modified Rankin Scale assessments should be made by a neurology 
professional or by qualified individuals according to a certification process.  
Note: Assessment of the mRS score should occur at all scheduled visits in a 
study; mRS also should be performed after a stroke and at 90 days after the onset 
of any stroke. 
TAV-IN-TAV 
DEPLOYMENT 
An additional valve prosthesis is implanted within a previously implanted 
prosthesis because of suboptimal device position and/or function during or after 
the index procedure. 

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Table 25.2-1: Definitions 
Term 
Definition 
TRANSIENT 
ISCHEMIC ATTACK 
(TIA) 
• Transient episode of focal neurological dysfunction caused by brain, spinal 
cord, or retinal ischemia, without acute infarction  
• Duration of a focal or global neurological deficit is <24 h  
• Neuroimaging does not demonstrate a new hemorrhage or infarct (if 
performed) 
Note: The difference between TIA and ischemic stroke is the presence of tissue 
damage or new sensory-motor deficit persisting >24 hours. By definition, TIA 
does not produce lasting disability. 
UNANTICIPATED 
ADVERSE DEVICE 
EFFECT  
Ref: 21CFR Part 812 
(UADE) 
 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the protocol 
or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
UNPLANNED USE OF 
CARDIOPUL-
MONARY BYPASS 
Unplanned use of cardiopulmonary bypass for hemodynamic support at any time 
during the TAVR procedure 
VALVE 
EMBOLIZATION 
The valve prosthesis moves during or after deployment such that it loses contact 
with the aortic annulus. 
VALVE 
MALPOSITIONING 
Includes valve migration, valve embolization, or ectopic valve deployment 
VALVE MIGRATION 
After initial correct positioning the valve prosthesis moves upward or downward 
within the aortic annulus from its initial position, with or without consequences 
(e.g., regurgitation). 
VALVE-RELATED 
DYSFUNCTION 
Mean aortic valve gradient ≥20 mmHg, EOA ≤0.9-1.1 cm2, and/or DVI <0.35 
AND/OR moderate or severe prosthetic valve aortic regurgitation (per VARC 
definition) 
VALVE-RELATED 
SYMPTOMS/CHF 
REQUIRING 
HOSPITALIZATION 
The need for hospitalization associated with valve-related symptoms or 
worsening CHF (NYHA Class III or IV) is intended to serve as a basis for 
calculation of a “days alive outside the hospital” endpoint. Included are heart 
failure, angina, or syncope due to aortic valve disease requiring intervention or 
intensified medical management; clinical symptoms of CHF with objective signs 
including pulmonary edema, hypoperfusion, or documented volume overload 
AND administration of intravenous diuresis or inotropic therapy, performance of 
aortic valvuloplasty, institution of mechanical support (intra-aortic balloon pump 
or ventilation for pulmonary edema), or hemodialysis for volume overload; clear 
documentation of anginal symptoms AND no clinical evidence that angina was 
related to coronary artery disease or acute coronary syndrome; documented loss 
of consciousness not related to seizure or tachyarrhythmia. 
VALVE 
THROMBOSIS 
Any thrombus attached to or near an implanted valve that occludes part of the 
blood flow path, interferes with valve function, or is sufficiently large to warrant 
treatment. Note that valve-associated thrombus identified at autopsy in a patient 
whose cause of death was not valve-related or at operation for an unrelated 
indication should not be reported as valve thrombosis. 
VASCULAR ACCESS 
SITE AND ACCESS 
Major Vascular Complications 
• Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, 
or new apical aneurysm/pseudoaneurysm  

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Table 25.2-1: Definitions 
Term 
Definition 
RELATED 
COMPLICATIONS 
• Access site or access-related vascular injury (dissection, stenosis, perforation, 
rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve 
injury, compartment syndrome, percutaneous closure device failure*) leading 
to death, life-threatening or major bleeding**, visceral ischaemia, or 
neurological impairment 
• Distal embolization (non-cerebral) from a vascular source requiring surgery or 
resulting in amputation or irreversible end-organ damage 
• The use of unplanned endovascular or surgical intervention associated with 
death, major bleeding, visceral ischaemia or neurological impairment 
• Any new ipsilateral lower extremity ischemia documented by patient 
symptoms, physical exam, and/or decreased or absent blood flow on lower 
extremity angiogram 
• Surgery for access site-related nerve injury 
• Permanent access site-related nerve injury 
Minor Vascular Complications 
• Access site or access-related vascular injury (dissection, stenosis, perforation, 
rupture, arterio-venous fistula, pseudoaneurysms, hematomas, percutaneous 
closure device failure*) not leading to death, life-threatening or major 
bleeding**, visceral ischaemia or neurological impairment 
• Distal embolization treated with embolectomy and/or thrombectomy and not 
resulting in amputation or irreversible end-organ damage 
• Any unplanned endovascular stenting or unplanned surgical intervention not 
meeting the criteria for a major vascular complication 
• Vascular repair or the need for vascular repair (via surgery, ultrasound-guided 
compression, transcatheter embolization, or stent-graft) 
*Percutaneous Closure Device Failure 
Failure of a closure device to achieve hemostasis at the arteriotomy site leading to 
alternative treatment (other than manual compression or adjunctive endovascular 
ballooning) 
Note: Pre-planned surgical access or a planned endovascular approach to vascular 
closure (e.g., “pre-closure”)99,100 should be considered as part of the TAVR 
procedure and not as a complication, unless untoward clinical consequences are 
documented (e.g., bleeding complications, limb ischemia, distal embolization, or 
neurological impairment). 
Note: If unplanned percutaneous or surgical intervention does not lead to adverse 
outcomes this is not considered a major vascular complication.  
** Refers to VARC bleeding definitions66,67 
VENTRICULAR 
SEPTAL 
PERFORATION 
Angiographic or echocardiographic evidence of a new septal perforation during 
or after the TAVR procedure 
VESSEL 
PERFORATION 
Unexpected puncture of the vessel with evidence of extravasation into 
extraluminal surrounding tissue or space requiring treatment using interventional 
or surgical techniques 
VULNERABLE 
SUBJECTS 
(per ISO 14155) 
Individuals who are unable to fully understand all aspects of the investigation that 
are relevant to the decision to participate, or who could be manipulated or unduly 
influenced as a result of a compromised position, expectation of benefits or fear 
of retaliatory response 

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Table 25.2-1: Definitions 
Term 
Definition 
Abbreviations: ADE=adverse device effect; AE=adverse event; AR=aortic regurgitation; AVA=aortic valve 
area; AVR= aortic valve replacement; CEC= Clinical Events Committee; CK= creatine kinase; 
CT=computed tomography; DVI=Doppler velocity index; ECG=electrocardiogram; EOA=effective orifice 
area; FEV= forced expiratory volume; GDPR= General Data Protection Regulation; LBBB=left bundle 
branch block; LV= left ventricle; MI=myocardial infarction; MRI=magnetic resonance imaging; 
NYHA=New York Heart Association; PPM=permanent pacemaker; RBC=red blood cell; SADE=serious 
adverse device effect; SAE=serious adverse event; TAV=transcatheter aortic valve; TAVR=transcatheter 
aortic valve replacement; TEE=transesophageal Doppler echocardiography; TIA=transient ischemic attack; 
URL=upper reference limit (defined as 99th percentile of normal reference range); VARC=Valve Academic 
Research Consortium 
 
26. Revision History 
26.1. Summary of Protocol Revision History 
Protocol revision history is provided in Table 26.1-1.

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
A 
12-Oct-2018 
90702637 
Rev/Ver AJ 
– 
Not applicable. 
– 
B 
10-Jan-2019 
90702637 
Rev/Ver AJ 
Section 2, Synopsis, 
Study Design 
• Roll-In Cohort: A non-randomized Roll-In phase… Centers 
with prior experience with ACURATE are not required to do 
Roll-In cases. Data… 
Clarify that centers 
with ACURATE 
experience are not 
required to do Roll-
In cases. 
Section 2, Synopsis, 
Method of 
Assigning… 
Roll-In Cohort: For centers… cohort. Centers with prior 
experience with ACURATE are not required to do Roll-In cases. 
Section 2, Synopsis, 
Inclusion Criteria 
IC1.  
 
Section 8.2, Table 
8.2-1, Inclusion 
Criteria IC1.  
Removed the following text: 
• Asymptomatic Subjects 
- Initial AVA ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) and 
maximal aortic velocity ≥5.0 m/s as measured by 
echocardiography and/or invasive hemodynamics 
Updated remaining text to read as follows: 
IC1. Subject has documented severe symptomatic native aortic 
stenosis defined as follows: aortic… 
Not applicable to 
approved devices. 
Section 5.1.3, 
Introducer Set 
It is recommended that… or the commercially available 14F 
iSLEEVE™ Introducer Set (iSLEEVE; Boston Scientific 
Corporation, Marlborough, MA, USA) be used as… The sheath 
component of the iSLEEVE is expandable, which allows for 
transient sheath expansion during delivery system introduction. 
The LIS S is suitable for use in subjects with femoral vascular 
access ≥6.0 mm. The 14F iSLEEVE is suitable for use in subjects 
with femoral vascular access ≥5.5mm. 
Added the 
iSLEEVE 
introducer. The 
iSLEEVE allows for 
entry into smaller 
femoral arteries and 
is expected to limit 
any tissue damage 
due to the transient 
nature of the 
expansion. 

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 7.1, Scale 
and Duration 
Roll-In Cohort: A non-randomized Roll-In phase… (in total). 
Centers with prior experience with ACURATE are not required to 
do Roll-In cases. Data… 
Clarify that centers 
with ACURATE 
experience are not 
required to do Roll-
In cases. 
Section 7.2, 
Treatment 
Assignment 
Note: Centers that do not have implantation experience with the 
ACURATE neo™ bioprosthesis (transfemoral delivery) will 
perform at least 2 non-randomized Roll-In cases before 
commencing enrollment in the randomized cohort. Centers with 
prior ACURATE experience may do Roll-In cases but are not 
required to do so. All… 
Section 7.3, 
Justification… 
…in the Roll-In phase of this study (centers without implantation 
experience with the ACURATE neo™ bioprosthesis [transfemoral 
delivery] are required to do 2 Roll-In cases each) and… 
Section 9.1.1,  
Roll-In Subjects 
There… bioprosthesis (transfemoral delivery) will perform at least 
2 Roll-In cases before commencing enrollment in the randomized 
cohort; centers with prior experience with ACURATE neo are not 
required to do Roll-In cases. For… 
Section 10.2.1, 
Strategies for 
Recruitment and 
Retention 
All efforts will be made… Investigators are encouraged to enroll 
subjects who are willing to comply with the follow-up 
requirements of the study. If a visit is missed, the center should 
attempt to contact the subject to reschedule the missed visit and 
counsel the subject on the importance of maintaining the assigned 
visit schedule. 
Clarify information 
around subject 
retention efforts. 
Section 10.7.2, 
ACURATE 
Transfemoral… 
…The commercially available LIS-S introducer or the 
commercially available 14F iSLEEVE introducer are 
recommended. 
Added the 
iSLEEVE 
introducer.  
Section 11.1.1.4, 
Statistical 
Methods… 
…in the SAP. Please also see Section 9.4, Section 10.1, and 
Section 10.2.1 regarding data collection and missing data. 
Clarify information 
around missing data. 
 

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 11.3.3, 
Subgroup Analyses 
for Randomized 
Subjects 
Added 2 more subgroups:  
• Age (<75 years and ≥75 years) 
• Any race and ethnicity category with >100 enrolled subjects as 
described in the SAP 
 
Treatment groups will also be compared in the age, race, and 
gender subgroup analyses. No adjustments… 
Additional 
subgroups requested 
by regulatory 
authority. 
Section 16.4.2, 
Training… 
Note: For centers… required proctored cases. Centers with prior 
experience with the ACURATE bioprosthesis who are proctor-free 
are not required to do Roll-In cases but may do Roll-In subjects 
without the presence of a proctor. 
Clarify that centers 
with ACURATE 
experience are not 
required to do Roll-
In cases. 
Section 25.2, 
Definitions 
 
REPEAT 
PROCEDURE FOR 
VALVE-RELATED 
DYSFUNCTION 
 
Any surgical…re-operations, enzymatic, balloon… or surgical 
AVR. 
 
Also removed the following text: 
• Conversion to open surgery 
• Conversion to… complications 
• Unplanned use of CPB 
• Unplanned use… procedure 
Text removed for 
clarity. 
C 
21-May-
2019 
90702637 
Rev/Ver AL 
First page 
Added the following: 
National Clinical Trial Identification Number: NCT03735667 
Required per 
protocol template 
version AL 
Page 2 
Added date of current version: 21-May-2019 
Updated protocol 
Section 2. Protocol 
Synopsis 
Additional Measurements: Added reference to VARC 3 
 
Inclusion Criteria: Updated as follows: 
Expected 
publication of 
updated VARC 3 
guidelines 
 

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
IC4. Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees 
that the subject has an on-label United States Food and Drug 
Administration (FDA) approved indication for TAVR is at 
intermediate risk or above for surgical valve replacement 
and TAVR is appropriate. The heart team should consider 
the Society of Thoracic Surgeons (STS) score as well as 
other factors including frailty, prior surgical history, 
malignancy or radiation therapy, pulmonary disease, renal 
disease, liver disease, neuromuscular disease, orthopedic 
disease, chest deformity, and aortic calcification. Subjects 
considered to be at intermediate surgical risk or above have 
a predicted risk of surgical mortality ≥ 3% based on the STS 
risk score and other clinical comorbidities unmeasured by 
the STS risk calculator. 
Updated per FDA 
suggestion 
Table 4.1-4 
Randomized Trials 
with ACURATE 
neo TF 
The ACURATE neo Aortic Bioprosthesis together with the 
ACURATE neo TF Delivery System are also undergoing clinical 
assessment in two prospective, multicenter RCTs (SCOPE I and 
SCOPE II) as shown in Table 4.1 4; enrollment is currently 
ongoing in both studies.  
SCOPE I: N=730 planned subjects randomized 1:1 Enrolling 
SCOPE II: N=764 planned subjects randomized 1:1 Enrolling 
Updated for clarity 
Section 6.5 
Additional 
Measurements 
Added a reference to VARC 3 
Additional measurements based on the VARC endpoints and 
definitions66-68 
Expected 
publication of 
updated VARC 3 
guidelines 
Section 7.1 Scale 
and Duration 
The ACURATE IDE study is will be registered at 
ClinicalTrials.gov (NCT03735667) prior to enrollment of the first 
subject. 
Registered the trial 
Section 8.2 
Inclusion Criteria 
Table 8.2-1 Inclusion Criteria updated as follows: 
Updated per FDA 
suggestion 

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IC4. Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees 
that the subject has an on-label United States Food and Drug 
Administration (FDA) approved indication for TAVR is at 
intermediate risk or above for surgical valve replacement 
and TAVR is appropriate. The heart team should consider 
the Society of Thoracic Surgeons (STS) score as well as 
other factors including frailty, prior surgical history, 
malignancy or radiation therapy, pulmonary disease, renal 
disease, liver disease, neuromuscular disease, orthopedic 
disease, chest deformity, and aortic calcification. Subjects 
considered to be at intermediate surgical risk or above have 
a predicted risk of surgical mortality ≥ 3% based on the STS 
risk score and other clinical comorbidities unmeasured by 
the STS risk calculator. 
Section 10.1 Data 
Collection 
Additional text as follows: 
This section indicates the data needed to fulfill the objectives of 
this clinical study. Boston Scientific Corporation considers data 
collected from clinical trial subjects to be personal data (see 
definitions of different data categories in Table 25.2 1) and 
compliance with privacy and data protection laws and regulations 
(for example, the General Data Protection Regulation [GDPR]) to 
be critically important. Data collection for this clinical study has 
been carefully considered to comply with data privacy laws.  
Include information 
on privacy 
considerations for 
clinical study data 
collection. 

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Section 18.1.1 
Reduced Leaflet 
Motion 
New section added: 
Reduced leaflet motion (RLM) suggestive of subclinical leaflet 
thrombosis, as detected by high-resolution CT, has been reported 
with bioprosthetic TAVR and SAVR valves85-88. It is less 
common among subjects receiving anticoagulant therapy and has 
been shown to resolve with such treatment85-91.   
Clinical signs of RLM include elevation of transvalvular gradients 
(as determined by echocardiography), central or peripheral 
thromboembolic events, and unexpected recurrence of heart 
failure. Computed tomography imaging is recommended to 
appropriately assess subjects with echocardiographic and/or 
clinical suspicion of leaflet thrombosis. Additional anticoagulant 
therapy may be indicated based on symptoms/signs and subject 
bleeding risk85-91. 
Updated per FDA 
suggestion 
Section 24 
Bibliography 
Added new references on reduced leaflet motion  
Support FDA 
suggestion 
Added new reference for VARC 3 
Expected 
publication of 
updated VARC 3 
guidelines 
Section 25.1 
Abbreviations 
Added abbreviations for “General Data Protection Regulation” 
(GDPR) and “reduced leaflet motion” (RLM).  
Clarification 
Section 25.2 
Definitions 
Added definitions for the following terms in Table 25.2-1: 
• Data Categories 
• General Data Protection Regulation 
 
Include information 
on privacy 
considerations for 
clinical study data 
collection 
Added a note to the definition of structural valve deterioration: 
Expected 
publication of 

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Note: Additional outcomes may be measured per definitions set 
in the most current VARC guidelines (as released at the time of 
analysis). 
updated VARC 3 
guidelines 
D 
31-Jul-2019 
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Contact Information 
Clinical Contact 
Lisa Currier 
Senior Clinical Trial manager… 
Sarah Zanon… 
Chemin de la Venoge 11  
Dornacherplatz 7 
4500 Solothurn, 1024 Ecublens, Switzerland 
Updated title; 
Updated address 
10.4 Screening 
Assessments 
Updated timing of screening imaging assessment for transthoracic 
echocardiography 
• Imaging assessments 
o Within 60 90 days prior… 
 
More closely align 
with what sites are 
doing for TTE 
assessments in 
clinical Standard of 
Care practice. 
16.4.2 Training with 
the Investigational 
Device 
Device Demonstration: A live or hands-on training to 
simulate/practice the implantation procedure with demonstration 
devices or in a bench model or a robotic simulation. 
Updated to clarify 
that demonstration 
devices can be used 
live to simulate the 
implantation  
18.1.1 Reduced 
Leaflet Motion… 
Reduced leaflet… therapy and in some cases has been shown… 
FDA request 
E 
08-Jan-2020 
90702637 
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Contact Information 
Beth Louh 
Clinical Trial Manager, Interventional Cardiology 
Boston Scientific Corporation 
100 Boston Scientific Way, Marlborough, MA  01752 USA 
Additional project 
manager 
Section 2, Synopsis, 
Study Design 
• Roll-In Cohort: A non-randomized Roll-In phase… will 
perform at least 2 Roll-In cases before commencing enrollment 
treatment in the randomized cohort. 
Clarify centers must 
have performed 2 
Roll-In cases before 

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Section 2, Synopsis, 
Method of 
Assigning Patients 
• Roll-In Cohort: For centers… at least 2 Roll-In subjects will 
be treated before commencing enrollment treatment in the 
randomized cohort. 
treating subjects in 
the randomized 
cohort. 
Section 2, Synopsis, 
Planned Number … 
Subjects will be enrolled at up to 50 65 centers… There will be up 
to 600630 subjects in ACURATE IDE… 
Cohort 
Number of Subjects 
Roll-In 
Up to 100 130 
 
Support faster 
enrollment  
Section 2, Synopsis, 
Adjunctive 
Pharmacologic 
Therapy 
Aspirin 
A loading dose of aspirin… is required recommended for 
subjects... The loading dose must should be administered prior to 
the implant procedure…. 
P2Y12 Inhibitor 
A loading dose of a P2Y12 inhibitor… is required recommended 
for subjects... The loading dose must should be administered prior 
to the implant procedure…. 
Note 5: If a subject requires chronic anticoagulation, either a 
P2Y12 inhibitor or aspirin is required recommended prior to and 
required after the implant procedure in addition to the 
anticoagulant therapy (but treatment with both aspirin and a P2Y12 
inhibitor after the implant procedure is are not required). 
Current standard of 
care; updated text 
for clarification 
Section 2, Synopsis, 
Inclusion Criteria 
IC4. Heart team… Note 8: At the time this protocol… and 
Canada. Subjects at low surgical risk were subsequently approved 
for TAVR with commercially available devices in the United 
States. 
Reflects the updated 
FDA approval of 
TAVR in low-risk 
patients. 
4.1.3 Clinical 
Studies with the 
ACURATE Aortic 
Bioprosthesis 
The ACURATE neo Aortic Bioprosthesis… multicenter RCTs 
(SCOPE I and SCOPE II) as shown in Table 4.1-4. 
To Table 4.1-4, added the following: 
SCOPE I: N=730 planned subjects; 739 subjects were randomized 
1:1 
SCOPE I results (30 
days) have been 
published.  

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Primary endpoint outcomes (30 days) have been reported for 731 
subjects72. 
SCOPE II: Primary endpoint outcomes (1 year) to be reported 
likely in the second half of 2020. 
Outcomes at 30 days in the SCOPE I trial are summarized in 
Table 4.1-5 below. The primary safety and efficacy composite 
endpoint at 30 days included…  The primary endpoint occurred in 
87 subjects (24%) in the ACURATE neo cohort and in 60 subjects 
(16%) in the SAPIEN 3 group; thus, non-inferiority of ACURATE 
neo was not met (absolute risk difference of 7.1% [upper 95% 
confidence limit: 12.0%], P=0.42). The difference was largely 
driven by a higher rate of PVR with ACURATE neo compared to 
SAPIEN 3. Notably, most of the individual clinical components of 
the primary endpoint were similar between the 2 groups as were 
secondary clinical endpoints (Table 4.1-5). 
< Table 4.1.5: SCOPE I – 30-Day Outcomes> added. 
The ACURATE neo2™ Transfemoral Aortic Valve System… 
N=120). Outcomes to 1 year73 are shown in Table 4.1-6. Clinical 
results showed sustained safety and performance comparable to 
other TAVR valves in similar patient populations. The observed 
hemodynamic improvement post index procedure was maintained 
at 1 year. Notably, PVR was mild or less in 97.5% of subjects at 1 
year. 
<Table 4.1-6: Outcomes to 1 Year in ACURATE neo AS TF 
Study (N=120)> added. 
Data to 1 year have 
been presented. 
7.1 Scale and 
Duration 
Subjects will be enrolled at up to 5065 centers… There will be up 
to 600630 subjects in… 
 
Roll-In Cohort: A non-randomized Roll-In phase… will perform 
at least 2 Roll-In cases before commencing enrollment treatment 
Increased number of 
centers to support 
faster enrollment 
 

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in the randomized cohort (up to 100 130 Roll-In subjects in 
total)... 
Clarify centers must 
have performed 2 
Roll-In cases before 
treating subjects in 
the randomized 
cohort. 
7.2 Treatment 
Assignment 
Note: Centers that do not have… will perform at least 2 Roll-In 
cases before commencing enrollment treatment in the randomized 
cohort. 
7.3 Justification for 
the Study Design 
There will be up to 600 630 subjects in ACURATE IDE … 
limiting the potential exposure of study subjects to risk, up to 
100130 subjects will be enrolled in the Roll-In phase… Up to 
5065 centers… 
Support faster 
enrollment 
Table 8.2-1 
IC4. Heart team… Note 2: At the time this protocol… and 
Canada. Subjects at low surgical risk were subsequently approved 
for TAVR with commercially available devices in the United 
States.  
Reflects the updated 
FDA approval of 
TAVR in low-risk 
patients. 
9.1.1 Roll-In 
Subjects 
There will be… will perform at least 2 Roll-In cases before 
commencing enrollment treatment in the randomized cohort; 
centers... 
Clarify centers must 
have performed 2 
Roll-In cases before 
treating subjects in 
the randomized 
cohort. 
9.2 Discontinuation 
of Study 
Intervention 
If a study valve is surgically explanted… followed for safety (no 
protocol-required echocardiography, electrocardiography or QOL 
assessment) through end of study. 
Clarify subjects 
without a study 
valve do not need 
protocol required 
ECG or QOL 
assessments  
10.1 Data Collection 
… Subjects who are enrolled but do not receive a study valve 
(test or control) will be followed for 1 year to assess for safety but 
do not need to have protocol required echocardiography, 
electrocardiography, or QOL assessments. If a study valve is 
surgically explanted, the subject will be followed for safety (no 
protocol required echocardiography, electrocardiography, or QOL 
assessments) through end of study. 

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Table 10.1-1 
Footnote b: All follow-up… do not need to have protocol-required 
TTE, ECG or QOL assessments. 
Table 10.1-1 
Footnote d: NIHSS and mRS… independent (not involved with 
the care of study subjects). In addition to the assessments noted in 
the table, there are additional requirements for administering 
NIHSS/mRS/neurological physical exams in subjects where 
stroke is suspected. A neurological physical exam… 
Clarify that there are 
additional 
assessment 
requirements for 
subjects who may 
have experienced a 
stroke.   
Table 10.1-1 
Assessment: Coronary angiogram/CT coronary angiogram 
Footnote j: A coronary angiogram/CT coronary angiogram must 
be performed… 
 
Footnote o: Procedural… for analysis. Rotational angiography of 
the valve frame is required with results sent to the core laboratory. 
Clarify that CT 
angiogram can be 
used for coronary 
assessment, which 
reflects current 
standard of care 
 
Clarify this is not 
required. 
Figure 10.1-1 
In the “Clinical & Anatomic Eligibility Criteria Assessment” 
column added “/CT Coronary Angiogram” to the “Coronary 
Angiogram” box 
Reflects current 
standard of care 
10.2 Study 
Candidate Screening 
Subjects will be evaluated… In the United States, the Centers for 
Medicare and Medicaid Services (CMS) currently require 
independent evaluations by 21 cardiac surgeons for 
reimbursement. 
Updated CMS 
regulations 
10.4 Screening 
Assessments 
• Clinical Assessments 
o Risk assessments: Society… In the United States, CMS 
currently requires independent evaluations by 21 cardiac 
surgeons for reimbursement. 

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10.4 Screening 
Assessments 
• Imaging Assessments 
o A coronary angiogram/CT angiogram must be performed.... 
Reflects current 
standard of care 
10.6 Pre-procedure 
Medication 
• Antiplatelet therapy… must be given is recommended prior to 
valve implantation. 
o Aspirin: A loading dose… is required recommended for 
subjects… The loading dose must should be administered 
prior to the implant procedure…. 
o P2Y12 Inhibitor: A loading dose… is required recommended 
for subjects… The loading dose must should be administered 
prior to the implant procedure…. 
Note: If a subject… or aspirin is required recommended prior to 
the implant procedure, but not both aspirin and a P2Y12 inhibitor 
are not required. 
Current standard of 
care; updated text 
for clarification 
10.7 Index 
Procedure 
The TAVR… In the United States, CMS coverage criteria 
currently require that both cardiac surgeon and interventional 
cardiologist members of the heart team… 
Updated CMS 
regulations 
10.7.1 Control 
Cohort 
The DFU… A final post-deployment aortogram of the ascending 
aorta (including rotational angiography of the valve frame) must 
be performed… 
Clarify rotational 
angiography of the 
valve frame is not 
required 
10.7.2 ACURATE 
Transfemoral… 
10.7.2.2 Preparing and Using the ACURATE Transfemoral Aortic 
Valve System 
7) A final post-deployment aortogram of the ascending aorta 
(including rotational angiography of the valve frame) must be 
performed… 
10.8 Post Index 
Procedure 
O If a subject is treated with anticoagulation, either a P2Y12 
inhibitor or aspirin is required after the implant procedure in 
addition to the anticoagulant therapy (but treatment with both 
aspirin and a P2Y12 inhibitor after the implant procedure is are not 
required). 
Current standard of 
care; updated text 
for clarification 

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10.9 Prior to…  
10.10.1 30-Day… 
10.10.2 6-Month… 
10.10.4 Annual…  
Added the following: 
• Weight  
Updated for clarity 
10.10.3 1-Year… 
Removed the following: 
• Height  
11.1 Endpoints 
Data will be summarized… Roll-In cohort (up to 100130 
subjects). 
Increased number of 
centers to increase 
enrollment rate 
11.3.3 Subgroup 
Analyses… 
• Valve type (ACURATE neo, ACURATE neo2, SAPIEN 3, 
CoreValve) 
Clarify subgroup 
analysis 
16.4.2 Training… 
Note: For centers that do not have implantation experience… at 
least 2 Roll-In cases will be performed before enrollment 
treatment can commence in the randomized cohort. 
Centers must have 
performed 2 Roll-In 
cases before 
treating subjects in 
the randomized 
cohort. 
19.1 Reportable… 
It is the responsibility of the investigator to assess and report to 
BSC any event that occurs in any of the following categories; 
reporting requirements are described below in Table 19.4-1. 
• 
All serious adverse events 
• 
All device-related adverse events and adverse device 
effects (through 12 months) 
• 
All study procedure-related adverse events 
To clarify that all 
AEs and ADEs are 
required to be 
reported through 12 
months. 
24 Bibliography 
Added new references 72 (Lanz) and 73 (Möllmann) 
New publications 
with ACURATE 
F 
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4.1.3 Clinical 
Studies with the 
 
Section removed in its entirety. 
Removed per FDA 
request.  

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ACURATE Aortic 
Bioprosthesis 
24 Bibliography 
Removed references 59 (Schäfer), 60 (Kempfert 2013), 61 
(Kempfert 2015), 62 (Börgermann), 63 (Möllmann 2017), 64 
(Möllmann 2018), 65 (Möllmann 2017), 66 (Schaefer), 67 
(Hamm), 68 (Mauri), 69 (Toggweiler), 70 (Husser), 71 (Kim), 72 
(Lanz), 73 (Möllmann 2019) 
G 
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90702637 
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2. Synopsis, Study 
Design 
Updated ACURATE IDE Study Design Overview figure to show 
follow-up to 10 years post index procedure. 
FDA request to 
extend study to 10 
years 
2. Synopsis, 
Additional 
Measurements 
Additional measurements… will be collected… and annually 
through 10 years post index procedure… 
• Safety endpoints… 
o 
Bleeding: Life-threatening… (through 5 years) 
o 
Major vascular complication (through 5 years) 
• Additional indications of prosthetic aortic valve performance 
as measured by transthoracic echocardiography (TTE; see 
Note 2 and Note 3 below) 
• Functional… (see Note 3 below) 
• Neurological… (see Note 4 below) 
- Modified Rankin… follow-up visits (see Note 4 below) 
Note 3: Echocardiography and NYHA assessment are not required 
in years 6, 8, and 9 (telephone follow-up only). 
Note 4: The mRS is required at all follow-up visits up to 5 years. 
For subjects… 
2. Synopsis, Follow-
up Schedule 
All subjects implanted… annually for up to 10 years post-
procedure... The visits at 30 days, 6 months, 1 ̶ 5 years, 7 years, 
and 10 years are to be an office/clinical or in-person visit but may 
be done in-hospital should the subject be admitted at the time. 
Telephone follow-up is allowed at 6, 8, and 9 years.  Procedures… 

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2. Synopsis, Study 
Duration 
Subjects implanted with a test or control device will be followed 
for 10 years after the index procedure. 
Enrollment is expected… approximately 24 months; therefore, the 
total study duration is estimated to be approximately 12 years. 
2. Synopsis, 
Participant Duration 
… study duration for each subject is estimated to be 
approximately 10 years. 
4.1.2 Transcatheter 
Aortic Valve… 
Newer-generation devices have aimed to address these 
limitations59. The ACURATE TA™ Aortic Bioprosthesis 
(Symetis SA, Ecublens, Switzerland) is a self-expandable nitinol 
TAVR stent housing a porcine bioprosthesis and placed in a supra-
annular position via transapical delivery60. The device was 
designed to allow easy and intuitive implantation (single operator). 
The ACURATE neo™ Aortic Bioprosthesis was subsequently 
developed for transfemoral (TF) use with the ACURATE neo™ 
TF Delivery System. ACURATE neo has a pericardial skirt on the 
interior and exterior of the stent body which serves to limit PVR60. 
Described below are clinical outcomes with the self-expanding 
Symetis ACURATE Aortic Bioprosthesis.   
Added for clarity 
6.5 Additional 
Measurements 
Additional measurements… collected… annually up to 10 years 
post index procedure… 
• Safety endpoints… 
o 
Bleeding: Life-threatening… (through 5 years) 
o 
Major vascular complication (through 5 years) 
• Functional status… (see Note 3 below) 
• Neurological status… 
o 
Modified Rankin… visits up to 5 years 
Note 3: Echocardiography and NYHA assessment are not required 
in years 6, 8, and 9 (telephone follow-up only). 
FDA request to 
extend study to 10 
years 

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6.6 Overview of 
Objectives… 
Table 6.6-1 
Safety measures at discharge, 30 days, 6 months, and annually up 
to 10 years post index procedure 
7.1 Scale and 
Duration 
Updated ACURATE IDE Study Design figure to show follow-up 
to 10 years post index procedure. 
9.5 End of Study 
Definition 
… All subjects who receive a test or control device will be evaluated at 
discharge or 7 days (whichever comes first), 30 days, 6 months and 
annually up to 10 years post index procedure. All Visits at 30 days, 6-
months, 1–5 years, 7 years and 10 years are office/in-person visits. 
Telephone follow-up is allowed at 6, 8, and 9 years. A subject’s 
participation in the study will be considered complete after the 10-year 
visit… 
10.1 Data Collection 
All subjects… will be evaluated at discharge or 7 days (whichever 
comes first), 30 days, 6 months, 1 year, and then annually through 
10 years post index procedure. Physical clinic visits or in-person 
follow-up visits are scheduled for appointed times after the date of 
the index procedure through 5 years and at 7 and 10 years. 
Telephone follow-up is allowed at 6, 8, and 9 years. It is 
important… 
Visits/telephone follow-up not completed will be considered… 
Visits/telephone follow-up completed outside… Each follow-up 
visit must… 
Table 10.1-1 Data Collection for ACURATE IDE updated to show 
extension of study to 10 years post index procedure  
Figure 10.1-1 Data Collection for ACURATE IDE updated to 
show extension of study to 10 years post index procedure 
10.2 Study 
Candidate Screening 
Subjects will be… In the United States, the Centers for Medicare and 
Medicaid Services (CMS) require independent evaluations by 2 cardiac 
surgeons for reimbursement. The heart team… 
Change to CMS 
requirements 

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10.10 Follow-up 
All subjects implanted with a study valve (test or control) will be 
evaluated via physical clinical visits per the schedule… 
Note 2: Where indicated in Table 10.1 1, the follow-up… 
Updated for clarity 
10.10.4 Annual 
Follow-up (±45 
Days)… 
Added “to 5 Years” to the section title 
All implanted subjects must be evaluated in person at 2, 3, 4, and 
5 years… 
10.10.5 Follow-up 
(±60 Days) at 7 and 
10 Years 
Added new section 10.10.5 
All implanted subjects must be evaluated in person at 7 and 10 
years after the index procedure, with a window of ±60 days. The 
following assessments must be completed. The ACURATE IDE 
eCRFs identify the specific data points to be collected. 
• NYHA classification 
• Current antiplatelet/anticoagulant (if applicable) 
• TTE, including assessment of effective orifice area, peak and 
mean aortic valve gradient pressure, aortic regurgitation 
assessment, peak aortic velocity, and LVEF per the 
Echocardiography Core Laboratory procedure guidelines. All 
TTEs must be forwarded to the core laboratory for independent 
analyses. 
Note: TTE must be done for all subjects who have a transcatheter 
valve implanted in the aortic position during the index procedure.   
• Serious adverse event (SAE, SADE, UADE, and relevant VARC 
events to be adjudicated by the CEC) assessment for test device(s) 
and device deficiencies assessment for test device(s) with 
associated treatment. 
Note: Relevant VARC events to be adjudicated by the CEC 
include the following: mortality, stroke, spontaneous myocardial 
infarction, acute kidney injury, repeat procedure for valve-related 
FDA Request to 
extend study to 10 
years 

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dysfunction, hospitalization for valve-related symptoms or 
worsening congestive heart failure (NYHA III or IV), new 
pacemaker, new onset atrial fibrillation or atrial flutter, prosthetic 
aortic valve malpositioning (valve migration, valve embolization, 
or ectopic valve deployment), TAV-in-TAV, prosthetic aortic 
valve thrombosis and endocarditis. 
10.10.6 Follow-up 
(±60 Days) at 6, 8 
and 9 Years 
Added new section 10.10.6 
All implanted subjects must be evaluated at 6, 7, and 9 years after 
the index procedure, with a window of ±60 days. This evaluation 
may be conducted by telephone. The following assessments must 
be completed. The ACURATE IDE eCRFs identify the specific 
data points to be collected. 
• Current antiplatelet/anticoagulant (if applicable) 
• Serious adverse event (SAE, SADE, UADE, and relevant VARC 
events to be adjudicated by the CEC) assessment for test device(s) 
and device deficiencies assessment for test device(s) with 
associated treatment. Please see Section 10.10.5 for a list of 
relevant VARC events. 
10.11 Study 
Completion 
All subjects who receive a test device will be evaluated at… 6 
months, and then annually up to 10 years post index procedure. 
All Visits in the first 5 years and at 7 and 10 years are office or in-
person visits. Evaluations may be conducted by telephone at 6, 8 
and 9 years. A subject’s participation in the study will be 
considered complete after the 10-year visit. 
11.1 Endpoints 
The randomized data from the ACURATE IDE trial and data from 
the randomized populations of the SCOPE I (NCT03011346) and 
SCOPE II (NCT03192813) trials (see Table 4.1 4) will… 
Added for clarity 

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11.2.4 Reporting 
Events 
For time based clinical events, the cut-off … for endpoints at 2-10 
year it will be 365 days times the number of years… 
FDA Request to 
extend study to 10 
years 
19.1 Reportable 
Events 
Based on the VARC… 
• Bleeding events: Life-threatening… (through 5 years)  
Vascular complications: major (including annular rupture; through 
5 years) 
Updated for clarity 
H 
06-Mar-20 
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10.10.6 Follow-up 
(±60 Days)… 
All implanted subjects must be evaluated at 6, 78, and 9 years… 
Updated for clarity 
16.4.2 Training 
with… 
Proctoring: The investigator and co-investigators as well as the 
scrub team will be proctored by an individual experienced with 
the ACURATE valve and TAVR physician on a minimum… 
Allow for non-
physician proctors 
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22-Apr-20 
90702637 
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History 
Moved Revision History Table from page 3 to new Table 26.1-1 
Revision History. 
Updated for clarity 
Synopsis, Study 
Design 
• 4D CT Imaging Substudy: Selected centers with the ability to 
perform high quality 4D computed tomography (CT) scans will 
include subjects in a 4D CT Imaging Substudy to assess the 
prevalence of reduced leaflet mobility and hypoattenuated 
leaflet thickening (HALT) and the relationship, if any, to 
clinical events. Subjects will be randomized to test 
(ACURATE) and control device 
Updated Study Design figure to include 4D CT Imaging 
Substudy 
4D CT Substudy 
added per FDA 
request 
Synopsis, Planned 
Number of 
Subjects… 
* A subset of subjects in the randomized cohort will also be 
enrolled in the 4D CT Imaging Substudy. 

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Synopsis, 
Additional 
Measurements 
• For subjects in the CT Imaging Substudy, assessments using 
4D CT at 30 days and 1 year will be done as listed below. 
Data will be evaluated by an independent CT core laboratory. 
- Assessment of leaflet mobility 
- Assessment of hypoattenuated leaflet thickening (HALT) 
- Assessment of leaflet thrombosis 
Synopsis, Method of 
Assigning… 
Randomized Cohort: A computer… to Control. A subset of 
subjects in the randomized cohort will also be enrolled in the 4D 
CT Imaging Substudy. 
Synopsis, Follow-up 
Schedule 
Note 5: For subjects in the CT Imaging Substudy, the visits at 
30 days and 1 year must be done in the clinic (or in-hospital). 
Synopsis, 
Adjunctive 
Pharmacologic 
Therapy 
Note 8: Subjects who are expected to undergo chronic 
anticoagulation therapy after the TAVR procedure are not eligible 
to be included in the 4D CT Imaging Substudy (see Additional 
Exclusion Criteria below). 
Synopsis, 
Additional 
Exclusion Criteria 
Added another row: 
Additional exclusion criteria apply to subjects considered for 
enrollment in the CT Imaging Substudy as listed below. 
AEC1.   Subject has eGFR <30 mL/min (chronic kidney disease 
stage IV or stage V). 
AEC2.   Subject has atrial fibrillation that cannot be rate 
controlled to ventricular response rate < 60 bpm. 
AEC3. 
Subject is expected to undergo chronic anticoagulation 
therapy after the index procedure. 
Note 12: Subjects treated with short-term anticoagulation post 
procedure can be included in the CT Imaging Substudy; in these 
subjects the 30-day imaging will be performed 30 days after 
discontinuation of anticoagulation. 

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Section 6.4 
Additional 
Measurements 
• For subjects in the 4D CT Imaging Substudy, assessments 
using 4D CT at 30 days and 1 year will be done as listed 
below. Data will be evaluated by an independent CT core 
laboratory and should be blinded to local investigators for 
cardiac valve findings (local reading should be only for non-
cardiac valve findings such as unexpected lung pathology; see 
Section 10.10.1 for additional information). 
- Assessment of leaflet mobility 
- Assessment of hypoattenuated leaflet thickening (HALT) 
- Assessment of leaflet thrombosis 
Section 7.1 Scale 
and Duration 
Added bullet: 
• 
4D CT Imaging Substudy: Select centers with the ability to 
perform high quality 4D computed tomography (CT) scans 
will include subjects from the randomized cohort in a 4D CT 
Imaging Substudy to assess the prevalence of reduced leaflet 
mobility and hypoattenuated leaflet thickening (HALT)64 and 
the relationship, if any, to clinical events. Centers should ask 
all eligible subjects to consider participation in the substudy. 
… 10 years post procedure. Implanted subjects participating in 
the 4D CT Imaging Substudy will undergo additional 4D CT 
assessment at 30 days and 1 year. Enrolled… 
Updated Figure 7.1-1 
Section 7.3 
Justification… 
…reporting). Selected centers with the ability to perform high 
quality 4D CT scans will include subjects from the randomized 
cohort in a 4D CT Imaging Substudy to assess the prevalence of 
reduced leaflet mobility and HALT64 and their relationship, if 
any, to clinical events. In addition… 
Section 8.2 
Inclusion… 
Subjects… is met. Centers participating in the 4D CT Imaging 
Substudy must have the ability to perform high quality 4D CT 

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scans; subjects in this substudy must meet none of the additional 
exclusion criteria listed in Table 8.3 2. 
Section 8.3 
Exclusion… 
Additional exclusion criteria apply to subjects considered for 
enrollment in the 4D CT Imaging Substudy as listed below in 
Table 8.3 2.  
New Table 8.3-2 …Additional Exclusion Criteria… 
Section 10.1 Data 
Collection 
Updated Table 10.1-1 and Figure 10.1-1 
Add row and footnote for 4D CT imaging of prosthetic valve 
s: This applies to subjects in the 4D CT Imaging Substudy. 
Please refer to the CT Core Laboratory procedure guidelines (see 
study Manual of Operations). Results must be sent to the CT 
Core Laboratory (see Section 13.3.2). 
Note: For subjects in the CT Imaging Substudy, the visits at 30 
days and 1 year must be done in the clinic (or in-hospital). 
Section 10.10.1 30-
Day Follow-up… 
Added bullet: 
• For subjects enrolled in the 4D CT Imaging Substudy, 
assessment of prosthetic valve leaflet mobility using 4D CT 
must be performed per the CT Core Laboratory 
(Section 13.3.2) procedure guidelines (see study Manual of 
Operations). All 4D CT scans for subjects enrolled in the 4D 
CT Imaging Substudy must be sent to the CT Core Laboratory 
for independent analyses.  
Note: The CT scans will be read by the CT Core Laboratory 
and will not be provided to local investigators except as per 
below. Local reading should be done only for non-cardiac 
valve findings such as unexpected lung pathology. A study CT 
scan can be unblinded upon investigator request based on any 
of the following if the event occurs within 2 weeks of the 
study CT scan.  
o Any neurological event 

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o Any potential embolic event 
o Any MI (ST segment elevation MI or non-ST segment 
elevation MI) 
o Increase in aortic regurgitation to moderate or severe 
o A change in echocardiographic parameters including an 
increase in mean gradient of >10 mmHg or a change in 
Doppler velocity index (DVI) of >0.05. 
If any of the above events occurs outside of the 2-week 
window around the study CT scan, the investigator must not 
be unblinded to the core laboratory assessment of the study 
CT scan and instead should perform a separate CT scan if 
clinically indicated. If an additional CT scan is performed 
for clinical indications, it should be sent to the CT Core 
Laboratory for analysis. 
Section 10.10.3 1-
Year Follow-up… 
Added bullet: 
• For subjects enrolled in the 4D CT Imaging Substudy, 
assessment of prosthetic valve leaflet mobility using 4D CT 
must be performed per the CT Core Laboratory procedure 
guidelines (see study Manual of Operations). The 4D CT scans 
done for the 4D CT Imaging Substudy must be sent to the CT 
Core Laboratory for independent analyses.  
Note: The CT scans will be read by the CT Core Laboratory 
and findings will not be provided to local investigators except 
as noted above. Local reading should be done only for non-
cardiac valve findings such as unexpected lung pathology. A 
study CT scan can be unblinded upon investigator request 
based on the conditions described in Section 10.10.1 if the 
event occurs within 2 weeks of the study CT scan 

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Section 13.3.2 CT 
and Angiography 
Core Laboratory 
…of Operations. Data from subjects in the 4D CT Imaging 
Substudy will also be evaluated by the independent CT core 
laboratory; procedure guidelines for 4D CT scanning are 
provided by the core laboratory in the Manual of Operations. 
Section 18.1.1 
Reduced Leaflet 
Motion/Leaflet 
Thrombosis 
Added paragraph: 
The subset of subjects undergoing 4D CT scans at 30 days and 1 
year, will be exposed to an additional radiation dose of about 20 
milliSieverts (mSv) which is equivalent to about 10 years’ worth 
of natural background radiation. The contrast dye used during the 
image acquisition can cause medical problems such as allergic 
reactions and increase the risk of worsening kidney function or 
failure. 
Added risk 
associated with 4D 
CT Imaging 
Substudy 
participation 
Section 25.2 
Definitions 
Remove definitions for structural valve deterioration and 
resheathing/repositioning 
Add definition for hypo-attenuated leaflet thickening (HALT) 
and reduced leaflet mobility/motion (RLM) 
Updated definitions 
Section 26.1 
Revision History 
Added new Section 26.1 Revision History 
Moved Revision History Table from page 3 to Table 26.1-1 
Revision History. 
Updated for clarity 
J 
18-Nov-
2020 
90702637 
Rev/Ver AO 
Page 1 
European Authorized Representative 
Boston Scientific International S.A. 
Le Val Saint-Quentin 
2 rue René Caudron, 78960 
Voisins le Bretonneux, France 
Australian Representative 
Boston Scientific Pty. Ltd. 
Building 1, Level 6 
191 O’Riordan Street 
Mascot, NSW 2020, Australia 
Added to allow for 
additional centers in 
Australia and 
Europe 

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Section 2 Study 
Design 
…regulations. The study… from the Institutional Review 
Board/Research Ethics Board/Human Research Ethics 
Committee/ Independent Ethics Committee 
(IRB/REB/HREC/IEC) and/or… 
Section 2 Synopsis 
Planned Number of 
Subjects… 
Subjects will be enrolled at up to 6585 centers in the United 
States, Canada, Australia, and Europe. There will be up to 630 
1220 subjects in… 
Randomized Cohort: 500 1050 
Roll: In Cohort: Up to 130170 
Revised statistical 
approach per 
discussion with 
FDA 
Section 2 Synopsis 
Primary Endpoint 
Removed Primary Safety Endpoint: Composite of all… 30 days. 
Renamed “Primary Effectiveness Endpoint” to “Primary 
Endpoint” and updated the definition as follows: 
Composite of all-cause mortality, and disabling all stroke, and 
rehospitalization† at 1 year. 
† Hospitalization for valve-related symptoms or worsening 
congestive heart failure (NYHA class III or IV); per VARC-2 
definition 
Section 2 Synopsis 
Adjunctive 
Pharmacologic 
Therapy 
Anti-Platelet Therapy 
Per US society guidelinesb, antiplatelet therapy with aspirin and a 
P2Y12 inhibitor is recommended…medications. ACURATE IDE 
study subjects must receive some antiplatelet therapy (aspirin 
and/or a P2Y12 inhibitor) for at least 1 month following valve 
implant (see below for recommended doses). It should be noted, 
however, that recent clinical evidence points to increased 
bleeding risk post TAVR among subjects receiving dual 
antiplatelet therapy or antiplatelet therapy plus anti-coagulation 
(among subjects indicated for anti-coagulation) c. 
Aspirin 
A loading… After the valve implant procedure, aspirin (the 
recommended aspirin dose of is ≥75 mg daily. Post TAVR, 
aspirin and/or a P2Y12 inhibitor) must be given… 
Updated for clarity; 
new reports on 
antiplatelet therapy 
and TAVR. 

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P2Y12 inhibitor 
A loading dose… After the valve implant procedure, a P2Y12 
inhibitor and/or aspirin is… 
Note 7: If a subject… recommended prior to and required after 
the implant procedure in addition to the anticoagulant therapy 
(but treatment with both aspirin and a P2Y12 inhibitor after the 
implant procedure is are not required recommended). After the 
implant procedure, the subject must should be treated… 
c: Nijenhuis VJ, et al. N Engl J Med 2020;382:1696–1707 
Brouwer J, et al. N Engl J Med 2020;383:1447–1457 
Section 2, Inclusion 
Criteria 
Protocol Version J: As of this update to the protocol (Version J), 
subjects in all surgical risk classes were approved for TAVR in 
the United States, Canada, Australia, and European countries. 
Updated for clarity 
Section 2, Synopsis 
Primary Safety 
Endpoint 
Removed Primary Safety Endpoint and the associated statistical 
measures (Statistical Hypothesis, Statistical Test, Sample Size 
Calculations, Success Criteria) 
Revised statistical 
approach per 
discussion with 
FDA 
Section 2, Synopsis 
Primary 
Effectiveness 
Endpoint Statistical 
Hypothesis 
In the randomized cohort, the primary effectiveness endpoint 
(composite of all-cause mortality, and disabling all stroke, and 
rehospitalization at 1 year) rate for the ACURATE group is non-
inferior to that for the Control group. 
Section 2, Synopsis 
Statistical Test for 
the Primary 
Effectiveness 
Endpoint 
A Farrington-Manning… primary effectiveness endpoint rate… 
…where PE… primary effectiveness endpoint rates… 
The primary analysis set for the primary effectiveness endpoint... 
Section 2, Synopsis 
Sample Size 
Parameters for the 
Primary 
The sample size calculation for the primary effectiveness 
endpoint is based on the following assumptions. 
• Expected rate for both arms = 1525.9% (based on weighted 
average of TAVR data; see Note 14 below) 

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Effectiveness 
Endpoint 
• Non-inferiority margin (Δ) = 6 9.1% (4035% relative to the 
expected rate) 
• Test significance level (α) = 0.025 (1-sided) 
• Test (ACURATE): Control ratio = 1:1 
• Power (1 minus ß) ≥ 85% = 90%  
• Expected rate of attrition = 5% 
• Total sample size = 1050 (525 per group) 
• Number of evaluable subjects per group = 499700† 
• Analyses: Two interim plus one final (see Note 15 below) 
Note 14: The estimated proportions of subjects by operative risk 
level is 10% extreme risk, 30% high risk, and 60% intermediate 
risk.  
Note 15: The Haybittle-Peto method is used to specify and 
calculate the alphas for the first interim, second interim, and final 
analyses as 0.0001, 0.0001, and 0.025, respectively. The first 
interim analysis is an administrative analysis for regulatory 
agency review after 350 randomized subjects have completed 1-
year follow-up. The second interim analysis is planned to occur 
after 850 randomized subjects have completed 1-year follow-up. 
The final analysis for the primary endpoint will be performed 
with 1-year data from all subjects. 
† The planned 730 subjects from the SCOPE I study and 764 
subjects from the SCOPE II study will form the analysis 
population for a total of 1,494 subjects for the primary 
effectiveness endpoint analysis. 
Section 2, Synopsis 
Success Criteria for 
the Primary 
Effectiveness 
Endpoint 
If the P value from the Farrington-Manning standardized test for 
non-inferiority is <0.025 for the final analysis, the rate of the 
primary effectiveness endpoint… primary effectiveness endpoint 
being less than delta (Δ). 

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Section 4.1.2 
Transcatheter… 
…application to lower risk patients25,26 and Two recent 
randomized… intermediate-risk and low-risk surgical… 
Currently, …inoperable or at intermediate low to high… 
Updated Table 4.1-1: 
Add 2 rows for PORTICO IDE (2020) study; add text "The 
PORTICO™ Transcatheter Aortic Heart Valve Implantation 
System is manufactured by Abbott Structural Heart, St. Paul, 
MN, USA." 
Updated literature 
information 
Section 5.2 Control 
Device  
…catheterization techniques, is commercially available in both 
the United States and Canada, and is approved… 
For clarity 
Section 6.2 Study 
Endpoints 
…study device. For the ITT randomized cohort analysis set, if a 
subject receives 2 valves, the subject is assigned to the group 
corresponding to the first valve received. For the implanted… 
Section 6.3 Primary 
Safety Endpoint 
Removed Primary Safety Endpoint 
Revised statistical 
approach per 
discussion with 
FDA 
Section 6.3 6.4 
Primary 
Effectiveness 
Endpoint 
The primary effectiveness endpoint is a composite of all-cause 
mortality, and disabling all stroke, and rehospitalization at 1 
year. The primary analysis set for the primary effectiveness 
endpoint is the ITT analysis set.  
Note: For the primary endpoint, rehospitalization includes 
hospitalization for valve-related symptoms or worsening 
congestive heart failure (NYHA class III or IV); per VARC-2 
definition 
Section 6.5 
Overview of 
Objectives… 
Table 6.6-1: Removed Primary Safety row. 
Updated Primary Safety and Effectiveness row as follows: 
Objective: Determine safety and effectiveness… 
Endpoint: 1-Year Composite: mortality, and disabling all stroke, 
and rehospitalization 
Section 7.1 Scale 
and Duration 
Subjects will be enrolled at up to 6585 centers in the United 
States, Canada, Australia, and Europe. There will be up to 630 

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1220 subjects in ACURATE IDE… There will be up to 500 
1050 subjects in the RCT. 
Section 7.1 Scale 
and Duration 
Roll-In Cohort: A non-randomized…  randomized cohort (up to 
130 170 Roll-In subjects in total). 
 
The study… from the Institutional Review Board/Research 
Ethics Board/Human Research Ethics Committee/ Independent 
Ethics Committee (IRB/REB/HREC/IEC) and/or… 
 
NOTE: The modification IRB/REB/HREC/IEC has been made 
wherever IRB/REB occurs in the document. 
To allow for centers 
in Australia and 
Europe 
Section 7.2.1 
Treatment and 
Control 
Update Table 7.2-1 
Column headings: Objective Treatment; Endpoint Device; 
Rationale for Endpoint, Device Description 
Correct headings 
and to allow for 
centers in Australia 
and Europe 
Control Device 
SAPIEN 3*; 
CoreValve* 
 
* Or future iteration 
Balloon-expandable SAPIEN 3… 
commercially available in both the 
United States, and Canada applicable 
region. 
Section 7.3 
Justification… 
There will be up to 630 1220 subjects in… study subjects to risk, 
up to 130 170 subjects will be enrolled in the Roll-In phase of 
this study (centers without… 2 Roll-In cases each) and 500 1050 
subjects will be randomized… Up to 65 85 centers in the United 
States, and Canada, Australia, and Europe will participate… 
Revised statistical 
approach per 
discussion with 
FDA 
Section 8.2  
Inclusion Criteria 
Added to Table 8.2-1: 
Protocol Version J: As of this update to the protocol (Version J), 
subjects in all surgical risk classes were approved for TAVR in 
the United States, Canada, Australia, and European countries. 
For clarity 

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Section 10.10 
Follow-up 
Note 1: A subject who has received… reached the ACURATE 
IDE effectiveness primary endpoint (1 year). 
 
Section 10.1 Data 
Collection 
Updated <Figure 10.1-1> to include up to 1220 subjects, 1050 
randomized, up to 170 Roll-In 
Table 10.1-1 footnote m: …Baseline QOLs should must be 
performed within 30 days prior to the index procedure 
Section 10.8 Post 
Index Procedure 
The following are to be performed post-procedure. 
• Per society guidelines antiplatelet therapy with aspirin and a 
P2Y12 inhibitor is … Subjects must be treated with antiplatelet 
therapy (aspirin and/or a P2Y12 inhibitor) for… physician 
choice. It should be noted, however, that recent clinical 
evidence points to increased bleeding risk post TAVR among 
subjects receiving dual antiplatelet therapy or antiplatelet 
therapy plus anti-coagulation (among subjects indicated for 
anti-coagulation)77,78. 
o After the valve implant procedure, aspirin (recommended 
dose of ≥75 mg daily) and/or a P2Y12 inhibitor must be 
given for… availability. The P2Y12 inhibitor choice and 
dosing should be per local standard of care. 
o After the valve implant procedure, a P2Y12 inhibitor is 
required for at least 1 month. 
o If a subject is treated with anticoagulation, either a P2Y12 
inhibitor or aspirin is required recommended after… (but 
treatment… is not required recommended). The subject 
must should be treated… 
Updated for clarity; 
new reports on 
antiplatelet therapy 
and TAVR. 
Section 10.10.1  
30-Day Follow-up 
• For subjects… analyses. 
Note: Images will be read in a standard fashion for cardiac 
and non-cardiac findings by the clinical center CT imaging 
specialist. Clinical guidelines support anticoagulation with 
warfarin or another vitamin K inhibitor as a Class I 
recommendation for patients with established valve 
thrombosis4,5. However, there is no established guidance 
Allow centers to 
request access to 
core lab findings if 
they think it is 
needed to address 
subject health. 

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for pharmaceutical management of subclinical leaflet 
thrombosis. If deterioration of subject health due to 
suspected thrombosis occurs, the clinical center may 
request an unblinding of the Core Laboratory findings. 
Note: The CT scans will be read… sent to the CT Core 
Laboratory for analysis.  
Section 10.10.3  
1-Year Follow-up 
• For subjects… analyses. 
Note: Images will be read in a standard fashion for cardiac and 
non-cardiac findings by the clinical center CT imaging 
specialist. Clinical guidelines support anticoagulation with 
warfarin or another vitamin K inhibitor as a Class I 
recommendation for patients with established valve 
thrombosis4,5. However, there is no established guidance for 
pharmaceutical management of subclinical leaflet thrombosis. 
If deterioration of subject health due to suspected thrombosis 
occurs, the clinical center may request an unblinding of the 
Core Laboratory findings. 
Note: The CT scans will be read… within 2 weeks of the study 
CT scan. 
Section 11.1 
Endpoints 
The randomized data from the ACURATE IDE trial and data 
from the randomized populations of the SCOPE I 
(NCT03011346) and SCOPE II (NCT03192813) trials will be 
used in for primary endpoint analyses. The study must meet both 
the primary safety endpoint (Section 11.1.1) and the primary 
effectiveness endpoint (Section 11.1.2) to claim study success; 
therefore, no adjustment is needed for multiplicity.  
Data will be summarized separately for subjects in the 
ACURATE IDE Roll-In cohort (up to 130 170 subjects). 
Revised statistical 
approach per 
discussion with 
FDA 
Section 11.1.1 
Primary Safety 
Endpoint 
Removed Primary Safety Endpoint and the associated statistical 
measures sections: Statistical Hypothesis, Statistical Test, 
Sample Size Calculations, Success Criteria 

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Section 11.1.1 
Primary 
Effectiveness 
Endpoint 
Renamed “Primary Effectiveness Endpoint” to “Primary 
Endpoint” and updated the text as follows: 
The primary effectiveness endpoint is the composite of all-cause 
mortality, and disabling all stroke, and rehospitalization† at 1 
year. The events… 
Note 1: For the primary endpoint, rehospitalization is 
hospitalization for valve-related symptoms or worsening 
congestive heart failure (NYHA class III or IV); per VARC-2 
definition 
Section 11.1.1.1 
Statistical 
Hypothesis for the 
Primary Effective-
ness Endpoint 
The statistical hypothesis is that the primary effectiveness 
endpoint (composite of all-cause mortality, all and disabling 
stroke, and rehospitalization at 1 year) rate… 
The null… primary effectiveness endpoint… 
…correspond to primary effectiveness endpoint rates… 
The primary analysis set for the primary effectiveness endpoint... 
Section 11.1.1.2 
Sample Size 
Parameters for the 
Primary 
Effectiveness 
Endpoint 
The sample size calculation for the primary effectiveness 
endpoint is based on the following assumptions. 
• Expected rate for both arms = 1525.9% (based on... see Note 2 
below) 
• Non-inferiority margin (Δ) = 6 9.1% (4035% relative to 
expected rate) … 
• Power (1 minus ß) ≥ 85% = 90%  
• Expected rate of attrition = 5% 
• Total sample size = 1050 (525 per group) 
• Number of evaluable subjects per group = 499 700† 
• Overall Analyses: Two interim plus one final population=1494 
(see Note 3 below) 
Note 2: The estimated proportions of subjects by operative risk 
level is 10% extreme risk, 30% high risk, and 60% intermediate 
risk.  

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Note 3: The Haybittle-Peto method is used to specify and 
calculate the alphas for the first interim, second interim, and final 
analyses as 0.0001, 0.0001, and 0.025, respectively. The first 
interim analysis is an administrative analysis for regulatory 
agency review after 350 randomized subjects have completed 1-
year follow-up visits. The second interim analysis is planned to 
occur after 850 randomized subjects have completed 1-year 
follow-up visits. The final analysis for the primary endpoint will 
be performed with 1-year data from all subjects. 
The randomized cohorts of the ongoing SCOPE I (N=730 
subjects planned, 365 per treatment group) and SCOPE II 
(N=764 subjects planned, 382 per treatment group) trials will be 
pooled to form the analysis population for the primary 
effectiveness endpoint (N=1494). 
Section 11.1.1.3 
Success Criteria for 
the Primary 
Effectiveness 
Endpoint 
A Farrington… as described in the statistical analysis plan 
(SAP). If… test for non-inferiority is <0.025 in the final analysis, 
the rate of the primary effectiveness endpoint… rate of the 
primary effectiveness endpoint being less than delta (Δ). 
Section 11.1.1.4 
Statistical Methods-
Primary 
Effectiveness 
Endpoint 
All subjects who are enrolled and randomized will be eligible for 
evaluation. Any events or hospitalizations occurring after 
enrollment but prior to the index procedure should be entered in 
the electronic data capture system. 
Handling of dropouts and missing data will depend on their 
frequency and the nature of the outcome measure. Sensitivity 
analyses (e.g., tipping-point analysis) will be performed to assess 
the impact of subjects with inadequate follow-up (i.e., missing 
data) on the primary endpoint and to assess the robustness of the 
conclusion of the primary analysis. A sensitivity analysis of the 
primary endpoint, including events occurring after enrollment 
but prior to the index procedure, will be performed. Statistical 

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models that account for censored data will be employed in 
appropriate circumstances (e.g., for time-to-event outcomes). 
Suspected invalid data will be queried and corrected in the 
database prior to statistical analysis. Additional information may 
be found in the SAP. Please also see Section 9.4, Section 10.1, 
and Section 10.2.1 regarding data collection and missing data. 
Procedures similar to that described in Section 11.1.1.4 and 
discussed in the SAP will be applied to analysis of the primary 
effectiveness endpoint. 
Section 11.2.1 
Analysis Sets 
…in the analysis.  For the ITT randomized cohort analysis set, if 
a subject receives 2 valves, the subject is assigned to the group 
corresponding to the first valve received. For the implanted… 
Updated for clarity 
Section 11.2.3 
Number of Subjects 
The number of subjects enrolled per investigational center should 
not exceed 180 without prior authorization by the sponsor. 
Updated per new 
protocol template 
Section 11.3 Data 
Analyses 
Baseline… analysis of the primary safety endpoint, primary 
effectiveness endpoint, and additional measurements. 
Revised statistical 
approach per 
discussion with 
FDA 
Section 11.3.2 
Interim/ 
Administrative 
Analyses 
There will be 2 interim analyses as described in the SAP. The 
Haybittle-Peto method is used to adjust the alpha-levels for the 
first interim, second interim, and final analyses to 0.0001, 
0.0001, and 0.025, respectively. The first interim analysis is an 
administrative analysis for regulatory agency review after 350 
randomized subjects have completed 1-year follow-up visits. The 
second interim analysis is planned to occur after 850 randomized 
subjects have completed 1-year follow-up visits. An 
administrative analysis for regulatory agency review after all 500 
ACURATE IDE randomized subjects have completed their 1-
year follow-up visits may be performed as described in the SAP. 
Additional… review. 
No formal interim analyses are planned for the purpose of 
stopping this trial early for effectiveness or futility. A Data … 
charter. 

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Section 11.3.3 
Subgroup Analyses 
• Valve type (ACURATE neo, ACURATE neo2, SAPIEN, 
CoreValve) 
Section 11.3.4 
Justification of 
Pooling 
Analyses for the primary safety and primary effectiveness 
endpoints will be presented using data pooled across studies (see 
Section 11.1.1 and Section 11.1.2) study centers. Poolability 
analyses across study centers and studies will be performed for 
the primary endpoints. The differences of treatment effects on 
the primary endpoints across study centers and between studies 
will be… 
Section 13.1 Data 
Collection… 
All access to the clinical database will be changed to “Read 
Only” after all data are either “Hard Locked” or “Entry Locked.” 
Once acceptance of the final study report or finalization of 
publications (as applicable) is received, final database storage 
and archiving activities can begin. When all closeout activities 
are completed, a request to the BSC Information Technology 
department is submitted to have the database locked or 
decommissioned and all database access revoked. 
Updated per new 
protocol template 
Section 13.3.1 
Echocardiography 
Core Laboratory 
An independent… Operations. This same independent core lab 
will also analyze echocardiography data from SCOPE I and 
SCOPE II (see Section 11.1.1.2 for additional information on the 
SCOPE I and SCOPE II trials). 
Revised statistical 
approach per 
discussion with 
FDA 
14.0 Deviations 
…by the Sponsor. The sponsor will not approve protocol 
waivers. 
Updated per new 
protocol template 
16.1 Statement of 
Compliance 
This clinical investigation is financed by the study sponsor. 
Before the investigational site can be “Authorized to Enroll,” the 
investigational site must enter into a Clinical Study Agreement 
with the sponsor that details the financing of the study as well as 
the rights and obligations of the investigational site and the 
investigator. 

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16.2 Investigator 
Responsibilities 
All investigators will provide their qualifications and experience 
to assume responsibility for their delegated tasks through up-to-
date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that 
may interfere with the conduct of the clinical study or 
interpretation of results. 
16.3 Institutional 
Review Board/ 
Research Ethics 
Board/Human 
Research Ethics 
Committee/ 
Independent Ethics 
Committee 
The investigational center will obtain the written and dated 
approval/favorable opinion of the Institutional Review 
Board/Research Ethics Board/Human Research Ethics 
Committee/ Independent Ethics Committee 
(IRB/REB/HREC/IEC) for the clinical… 
 
NOTE: The modification IRB/REB/HREC/IEC has been made 
wherever IRB/REB occurs in the document. 
17 Monitoring 
…and appropriate regulatory authorities. The sponsor will put a 
plan in place to document the specific monitoring requirements.  
The study… 
19.1 Reportable 
Events… 
Any AE reportable event required… 
Section 19.2 
Definitions and 
Classification 
Updated Table 19.2-1: 
Serious Health Threat: Signal from any adverse event or device 
deficiency that indicates an imminent risk of death or a serious 
deterioration in the health of subjects, users or other persons, and 
that requires prompt remedial action for other subjects, users or 
other persons. 
Note 1: This would include events that are of significant and 
unexpected nature such that they become alarming as a potential 
serious health hazard or possibility of multiple deaths occurring at 
short intervals. 

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The following definitions will be used for defining hospitalization 
or prolongation of hospitalization for SAE classification purposes: 
Hospitalization: Hospitalization does not include: 
• Emergency room visit that does not result in in-patient 
admission  
Note 1: Although an emergency room visit does not itself 
meet the definition for hospitalization, it may meet other 
serious criteria (e.g., medical or surgical intervention to 
prevent permanent impairment or damage) 
• Elective and pre-planned treatment/surgery for a pre-
existing condition that is documented in the subject’s record 
at the time of consent/enrollment 
• Admission for social reasons and/or respite care in the 
absence of any deterioration in the subject’s general 
condition (e.g., subject is homeless, caregiver relief) 
• Pre-planned, protocol-specified admission related to the 
clinical study (e.g., procedure required by protocol) 
Prolongation of Hospitalization: In-patient admission to the 
hospital that is prolonged beyond the expected standard duration 
for the condition under treatment. 
Note 1: New adverse events occurring during the hospitalization 
are evaluated to determine if they prolonged hospitalization or 
meet another SAE criterion. 
19.5.1 Boston 
Scientific Device 
Deficiencies 
Device deficiencies that did not lead to an AE but could have led 
to a SAE if a) suitable action had not been taken, or b) 
intervention had not been made, or c) circumstances had been 
less fortunate must be reported as described in Table 19.4 1. 
21.1 Safety 
Monitoring Process 
To promote early detection of safety issues, the Clinical Events 
Committee (CEC) and Data Monitoring Committee (DMC; see 
below) will provide evaluations of safety events. Success of this 

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program requires dynamic collection of unmonitored data as 
soon as the event is reported. This is expedited through the 
Sponsor or designee, which is responsible for coordinating the 
collection of information for the subject dossier from the centers 
and core laboratories. The BSC personnel from the Medical 
Safety and Safety Trial Operations teams review safety data as 
they are reported by the centers throughout the duration of the 
study. During regularly scheduled monitoring activities, clinical 
research monitors will further support the dynamic reporting 
process this review through their review of source documents 
and other data information. The BSC Medical Safety and Safety 
Trial Operations teams group includes physicians health care 
providers with expertise… 
Section 21.1.1 
Clinical Events… 
…the CEC Charter. This same CEC will also adjudicate clinical 
event data from SCOPE I and SCOPE II (see Section 11.1.1.2 for 
additional information on the SCOPE I and SCOPE II trials). 
Revised statistical 
approach per 
discussion with 
FDA 
22.1.1 Criteria for 
Premature 
Termination… 
Possible reasons for premature study termination include, but are 
not limited to, the following. 
• Suspicion of an unacceptable risk. In this case, the sponsor 
shall suspend the clinical investigation while the risk is assessed. 
The sponsor shall terminate the clinical investigation if an 
unacceptable risk which cannot be controlled is confirmed. The 
occurrence of unanticipated adverse device effects that present a 
significant or unreasonable risk to subjects enrolled in the study 
• Instructions by the IRB/REB/HREC/IEC or regulatory 
authorities to suspend or terminate the clinical investigation. 
• An enrollment… 
Updated per new 
protocol template 
Section 23 Study 
Registration and 
Results 
Updated Section 23 as follows: 
23.1 Study Registration 
To comply with applicable laws and regulations, the study has 

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been registered on the publicly accessible database 
ClinicalTrials.gov (NCT03735667). 
23.2 Clinical Investigation Report 
Study results will be made available in accordance with the legal 
requirements and the recognized ethical principles, in accordance 
with the Boston Scientific Policy. A Clinical Investigation 
Report will be made available to all investigators, IRB/REB/ 
HREC/IEC and regulatory authorities, as applicable in 
accordance with the Boston Scientific Policy and local 
requirements.  As applicable an abbreviated Clinical 
Investigation Report will be made available on a publicly 
accessible database. 
23.3 Publication Policy 
Boston Scientific Corporation requires… 
Section 24 
Bibliography 
Added new references: 
29. Mack MJ… Transcatheter aortic… balloon-expandable valve 
in low-risk patients… 
30. Popma JJ… Transcatheter aortic… self-expanding valve in 
low-risk patients… 
33. Bonow RO… Appropriate use… 
38. Makkar RR… Self-expanding intra-annular… (PORTICO 
IDE): a randomised… 
77. Brouwer J… Aspirin with or without clopidogrel… 
78. Nijenhuis VJ… Anticoagulation with or without 
clopidogrel… 
Updated literature 
information 
K 
23-Mar-
2021 
90702637 
Rev/Ver AO 
Section 2, Synopsis 
Study Design 
Roll-In Cohort: A non-randomized… (transfemoral delivery; 
Symetis SA, Ecublens, Switzerland Boston Scientific 
Corporation, Marlborough, MA, USA) will perform… 
Change in legal 
manufacturer 

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Section 2, Synopsis 
Planned Number of 
Subjects… 
There will be up to 1220 1670 subjects… 
Cohort 
Number of Subjects 
Randomized 
1050 1500* 
Roll-In 
Up to 170 
* A subset of subjects (minimum of 200) in the randomized 
cohort will also be enrolled in the 4D CT Imaging Substudy. 
To achieve sufficient distribution of lower risk subjects, there 
will be ≥ 30% intermediate risk and ≥ 35% low risk randomized 
subjects enrolled. 
Per discussion with 
FDA, added cohort 
with low surgical 
risk. Updates 
regarding subject 
number and 
statistical approach 
are provided. 
 
Other changes have 
been made for 
clarity or to update 
guideline references. 
Section 2, Synopsis 
Study Duration 
Enrollment is expected to be completed in approximately 24 36 
months; therefore, the total study duration is estimated to be 
approximately 12 13 years. 
Section 2, Synopsis 
Adjunctive 
Pharmacologic… 
…daily. Post TAVR, aspirin and/or a P2Y12 inhibitor must be 
given for at least 1 month. It is recommended that daily aspirin 
be given indefinitely thereafter as per local standard of care. 
b: Otto CM, et al. J Am Coll Cardiol. 2021;77:e25-e197 
Holmes… e1159-e96 
Section 2, Synopsis 
Inclusion Criteria 
IC4. Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees 
that the subject is indicated for TAVR, is likely to benefit from 
at intermediate risk or above for surgical valve replacement, and 
TAVR is appropriate. The heart team should consider the 
Society of Thoracic Surgeons (STS) score as well as other 
factors including frailty, prior surgical history, malignancy or 
radiation therapy, pulmonary disease, renal disease, liver 
disease, neuromuscular disease, orthopedic disease, chest 
deformity, and aortic calcification. Subjects considered to be at 
intermediate surgical risk or above have a predicted risk of 
surgical mortality ≥ 3% based on the STS risk score and other 
clinical comorbidities unmeasured by the STS risk calculator. 

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Note 10: Risk of operative mortality must be assessed via an in-
person evaluation by a center cardiac surgeon and must be 
confirmed by the CRC (which must include an experienced 
cardiac surgeon). 
Note 11: At the time this protocol was written, subjects at 
extreme and high surgical risk were approved for TAVR with 
commercially available devices in the United States and 
Canada. Subjects at intermediate surgical risk were approved 
for TAVR with select commercially available devices in the 
United States and Canada. Subjects at low surgical risk were 
subsequently approved for TAVR with commercially available 
devices in the United States. 
IC5. Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees 
that the subject is likely to benefit from valve replacement. 
IC65. Subject… 
IC76. Subject, family… 
IC87. Subject is expected… 
db: Otto CM, et al. J Am Coll Cardiol. 2021;77:e25-e197 
Nishimura RA, et al. J Am Coll Cardiol. 2014;63:e57–185 
Protocol Version J: As of this update to the protocol (Version J), 
subjects in all surgical risk classes were approved for TAVR in 
the United States, Canada, Australia, and European countries. 
Section 2, Synopsis 
Statistical Test 
Method 
A Farrington-Manning standardized test will be used to test the 
one-sided The statistical hypothesis is that the primary endpoint 
rate for… 
A Bayesian analysisd will be performed to estimate the treatment 
difference between ACURATE and Control through posterior 
probability. Details are shown below.  
d: Popma JJ, et al. N Engl J Med 2019;380:1706-15 
Reardon MJ, et al. N Engl J Med 2017;376:1321-31  

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Section 2, Synopsis 
Sample Size 
Parameters… 
Although the primary endpoint analysis is performed using the 
Bayesian method, the sample size calculation (see Note 12 below) 
is based on a standard non-inferiority two-sample test approach. 
The sample size calculation for the primary endpoint is based on 
the following assumptions. 
• Expected rate for both arms = 25.922.3% (based on weighted 
average of TAVR datae; see Note 13 below) 
• Non-inferiority margin (Δ) = 9.18.0% (3536% relative to the 
expected rate) 
• Test significance level (α) = 0.025 (1-sided) (see Note 14 
below) 
• Test (ACURATE): Control ratio = 1:1 
• Power (1 minus ß) = ≥ > 90%  
• Expected rate of attrition = 5% 
• Total sample size = 10501500 (525750 per group) 
• Number of evaluable subjects per group = 499712 
• Analyses: Two One administrative, one formal interim, plus 
one final (see Note 15 below) 
Note 125: The Haybittle-PetoPocock-type methodf is used during 
sample size calculations. The statistical software EAST® 6.5 is 
used for the sample size calculations. 
Note 134: The estimated proportions of subjects by operative risk 
level is 10% extreme risk, 3025% high risk, and 630% 
intermediate risk, and 35% low risk.  
Note 14: A statistically equivalent posterior probability threshold 
for the Bayesian analysis is empirically chosen through extensive 
simulations and is pre-specified in the Statistical Analysis Plan 
(SAP). 

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Note 15: The Haybittle-Peto method is used to specify and 
calculate the alphas for the first interim, second interim, and final 
analyses as 0.0001, 0.0001, and 0.025, respectively. The first 
administrative interim analysis will be conducted when the first is 
an administrative analysis for regulatory agency review after 350 
randomized subjects have completed 1-year follow-up. The 
second formal interim analysis will be carried out after enrollment 
in the randomized cohort is completed. This formal interim 
analysis will be conducted on the full N=1500 randomized subject 
cohort when a subset of the is planned to occur after 850 
randomized subjects have completed 1-year follow-up (pending 
regulatory approval). The piecewise exponential modelg based on 
outcomes among these subjects will be used to predict the 1-year 
results by treatment group for the remaining enrolled subjects. The 
Bayesian method will be used to perform the hypothesis testing on 
the combined data sets. The A final analysis for the primary 
endpoint will be performed on all subjects with completed 1-year 
data if non-inferiority cannot be claimed at the formal interim 
analysis (see Success Criteria below) from all subjects. 
e: Adams DH, et al. N Engl J Med 2014;370:1790-8 
 
Leon MB, et al. N Engl J Med 2010;363:1597-607 
 
Leon MB, et al. N Engl J Med 2016;374:1609-20 
 
Mack MJ, et al. N Engl J Med 2019;380:1695-705 
 
Popma JJ, et al. J Am Coll Cardiol 2014;63:1972-81 
 
Popma JJ, et al. N Engl J Med 2019;380:1706-15 
 
Reardon MJ, et al. N Engl J Med 2017;376:1321-31 
 
Smith CR, et al. N Engl J Med 2011;364:2187-98 
 
Thourani VH, et al. Lancet 2016;387:2218-25 
 
Waksman R, et al. J Am Coll Cardiol Intv 2019;12:901–7 
 
Webb JG, et al. J Am Coll Cardiol Intv 2015;8:1797-806 
 
Medtronic CoreValve System PMA P130021/S002: FDA 
Summary of Safety and Effectiveness Data 

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f: Lan KKG and DeMets DL. Biometrika 1983;70:659–63 
g: Popma JJ, et al. N Engl J Med 2019;380:1706-15 
Section 2, Synopsis 
Success Criteria for 
the Primary 
Endpoint 
The Bayesian method is used to test the non-inferiority 
hypothesis of the primary endpoint. To establish that the 
ACURATE device is non-inferior to the Control, the results will 
need to meet the following equation: 
 
Pr(H1 | Data) > ξ   
where  
• Pr(H1 | Data) is the posterior probability of H1 given the 
observed data at either the interim or the final analysis; 
• H1 is the alternative hypothesis for non-inferiority: 
PE_ACURATE  minus PE_Control < Δ; 
• ξ is a prespecified threshold, which is empirically chosen 
through extensive simulations using the Bayesian approach for 
the non-inferiority tests.  
If non-inferiority has been declared at the formal interim 
analysis, the non-inferiority test will not be performed at the final 
analysis. If non-inferiority cannot be declared at this interim 
analysis, the non-inferiority test will be performed at the final 
analysis for all subjects using the Bayesian method with the same 
pre-specified threshold. The study will not stop for futility at the 
interim analysis. 
The detailed study operating characteristics and simulation 
results will be provided in the SAP.  
If the P value from the Farrington-Manning standardized test for 
non-inferiority is <0.025 for the final analysis, the rate of the 
primary endpoint for ACURATE will be concluded to be non-
inferior to the Control rate. This corresponds to the one-sided 
upper 97.5% confidence bound on the difference between 
treatment groups (ACURATE minus Control) for the observed 
rate of the primary endpoint being less than delta (Δ). 

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Section 4 
Introduction 
This protocol… manufactured by Symetis SA, an indirect 
subsidiary of Boston Scientific Corporation, Marlborough, MA, 
USA Ecublens, Switzerland. 
Section 4.1.2 
Transcatheter… 
<<Table 4.1-1 TAVR Outcomes…>> 
Updated table with references on outcomes in low risk subjects. 
Section 5.1 
ACURATE… 
The investigational… is designed by Symetis SA, an indirect 
subsidiary of Boston Scientific Corporation, Marlborough, MA, 
USA Ecublens, Switzerland. It is… 
Section 5.1.1 
ACURATE… 
The ACURATE… Bioprosthesis (Symetis SA, Ecublens, 
Switzerland Boston Scientific Corporation, Marlborough, MA, 
USA). There… 
Section 5.1.2 
ACURATE… 
…Delivery System (Symetis SA, Ecublens, Switzerland Boston 
Scientific Corporation, Marlborough, MA, USA). 
Section 5.1.3 
Introducer Set 
Note: In countries where the iSLEEVE and LIS-S are approved, 
the commercial device will be used. They will be considered 
investigational devices in countries where they are not approved. 
Section 6.4 
Additional 
Measurements 
• For subjects… Data will be evaluated by an independent CT core 
laboratory and should be blinded to local investigators for cardiac 
valve findings (local reading should be only for non-cardiac valve 
findings such as unexpected lung pathology; see Section 10.10.1 
for additional information).(See Note 5 below). 
Note 5: Images will be read in a standard fashion for cardiac and 
non-cardiac findings by the clinical center CT imaging specialist. 
Clinical guidelines support anticoagulation with warfarin or 
another vitamin K inhibitor as a Class I recommendation for 
patients with established valve thrombosis4,5. However, there is no 
established guidance for pharmaceutical management of 
subclinical leaflet thrombosis. If deterioration of subject health 

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due to suspected thrombosis occurs, the clinical center may 
request an unblinding of the Core Laboratory findings. 
Section 7.1 Scale 
and Duration 
Subjects will be enrolled at up to 85 centers in the United States, 
Canada, Australia, and Europe. There will be up to 1220 1670 
subjects in ACURATE IDE. It is expected that >80% of enrolled 
subjects will be from the United States. To achieve sufficient 
distribution of lower risk subjects, there will be ≥ 30% 
intermediate risk and ≥ 35% low risk randomized subjects enrolled 
(please see definition of operative risk in Section 25.2). 
• Randomized Cohort: A prospective… up to 10501500 subjects… 
• 4D CT Imaging Substudy: Select… include subjects (minimum 
of 200) from… 
All subjects … Enrollment is expected to be completed in 
approximately 36 months; therefore, the total study duration is 
estimated to be approximately 13 years. The study duration for 
each subject is expected to be approximately 10 years… 
Section 7.3 
Justification… 
There will be up to 1220 1670 subjects… In order… and 1050 
1500 subjects will be randomized… post index procedure. To 
achieve sufficient distribution of lower risk subjects, there will 
be ≥ 30% intermediate risk and ≥ 35% low risk randomized 
subjects enrolled. Per… aspirin and/or a… 
Section 8.2 
Inclusion Criteria 
IC4. Heart team… the subject is indicated for TAVR, is likely to 
benefit from valve replacement, at intermediate risk or above for 
surgical valve replacement and TAVR is appropriate. The heart 
team should consider the STS score as well as other factors 
including frailty, prior surgical history, malignancy or radiation 
therapy, pulmonary disease, renal disease, liver disease, 
neuromuscular disease, orthopedic disease, chest deformity, and 
aortic calcification. Subjects considered to be at intermediate 
surgical risk or above have a predicted risk of surgical mortality 

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Changes 
≥ 3% based on the STS risk score and other clinical 
comorbidities unmeasured by the STS risk calculator. 
Note 1: Risk of operative mortality must be assessed via an in-
person evaluation by a center cardiac surgeon and must be 
confirmed by the CRC (which must include an experienced 
cardiac surgeon). 
Note 2: At the time this protocol was written, subjects at extreme 
and high surgical risk were approved for TAVR with 
commercially available devices in the United States and Canada. 
Subjects at intermediate surgical risk were approved for TAVR 
with select commercially available devices in the United States 
and Canada. Subjects at low surgical risk were subsequently 
approved for TAVR with commercially available devices in the 
United States. 
 
IC5. Heart team (which must include an experienced cardiac 
interventionalist and an experienced cardiac surgeon) agrees that 
the subject is likely to benefit from valve replacement. 
 
Protocol Version J: As of this update to the protocol (Version J), 
subjects in all surgical risk classes were approved for TAVR in 
the United States, Canada, Australia, and European countries. 
Section 10.1 Data 
Collection 
<<Figure 10.1-1 Data Collection…>> 
Updated figure. 
Section 11.1.1.1 
Statistical 
Hypothesis… 
The statistical hypothesis… analysis sets). 
A Bayesian analysis will be performed to estimate the treatment 
difference between ACURATE and Control through posterior 
probability. Additional information is provided below. 
Section 11.1.1.2 
Sample Size 
Parameters… 
Although the primary endpoint analysis is performed using the 
Bayesian method, the sample size calculation (see Note 2 below) 
is based on a standard non-inferiority two-sample test approach. 
The…assumptions. 

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• Expected rate for both arms = 25.922.3% (based on a weighted 
average of TAVR data; see Note 23 below) 
• Non-inferiority margin (Δ) = 9.18.0% (365% relative to 
expected rate) 
• Test significance level (α) = 0.025 (1-sided) (see Note 4 
below) 
• Test (ACURATE): Control ratio = 1:1 
• Power (1 minus ß) = >90% 
• Expected rate of attrition = 5% 
• Total sample size = 1050 1500 (525 750 per group) 
• Number of evaluable subjects per group = 499 712 
• Analyses: Two One administrative, one formal interim, plus 
one final (see Note 3 5 below) 
 
Note 23: The Haybittle-Peto Pocock-type method is used for 
sample size calculations.to specify and calculate the alphas for 
the first interim, second interim, and final analyses as 0.0001, 
0.0001, and 0.025, respectively. The first interim analysis is an 
administrative analysis for regulatory agency review after 350 
randomized subjects have completed 1-year follow-up visits. The 
second interim analysis is planned to occur after 850 randomized 
subjects have completed 1-year follow-up visits. The final 
analysis for the primary endpoint will be performed with 1-year 
data from all subjects. The statistical software EAST® 6.5 is 
used for the sample size calculations. 
 
Note 23: The estimated proportions of subjects by operative risk 
level is 10% extreme risk, 3025% high risk, and 6030% 
intermediate risk, and 35% low risk. 
Note 4: A statistically equivalent posterior probability threshold 
for the Bayesian analysis is empirically chosen through extensive 

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simulations and is pre-specified in the Statistical Analysis Plan 
(SAP). 
Note 5: The administrative interim analysis will be conducted 
when the first 350 randomized subjects have completed 1-year 
follow-up. The formal interim analysis will be carried out after 
enrollment in the randomized cohort is completed. This formal 
interim analysis will be conducted on the full N=1500 
randomized subject cohort when a subset of the randomized 
subjects has completed 1-year follow-up (pending regulatory 
approval). The piecewise exponential model30 based on 
outcomes among these subjects will be used to predict the 1-year 
results by treatment group for the remaining enrolled subjects. 
The Bayesian method will be used to perform the hypothesis 
testing on the combined data sets. A final analysis will be 
performed on all subjects with completed 1-year data if non-
inferiority cannot be claimed at the formal interim analysis (see 
Section 11.1.1.3). 
Section 11.1.1.3 
Success Criteria… 
A Farrington-Manning standardized test will be used to test the 
hypothesis of non-inferiority in the difference between the rates 
of the two treatment groups, as described in the statistical 
analysis plan (SAP). If the P value from the Farrington-Manning 
standardized test for non-inferiority is <0.025 in the final 
analysis, the rate of the primary endpoint for the ACURATE 
group will be concluded to be non-inferior to the Control rate. 
This corresponds to the one-sided upper 97.5% confidence 
bound on the difference between treatment groups (ACURATE 
minus Control) for the observed rate of the primary endpoint 
being less than delta (Δ). The Bayesian method is used to test the 
non-inferiority hypothesis of the primary endpoint. To establish 
that the ACURATE device is non-inferior to the Control, the 
results will need to meet the following equation: 
 
Pr(H1 | Data) > ξ   

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where  
• Pr(H1 | Data) is the posterior probability of H1 given the 
observed data at either the interim or the final analysis;  
• H1 is the alternative hypothesis for non-inferiority: 
PE_ACURATE  minus PE_Control < Δ; 
• ξ is a prespecified threshold, which is empirically chosen 
through extensive simulations using the Bayesian approach for 
the non-inferiority tests.  
 
If non-inferiority has been declared at the formal interim 
analysis, the non-inferiority test will not be performed at the final 
analysis. If non-inferiority cannot be declared at this interim 
analysis, the non-inferiority test will be performed at the final 
analysis for all subjects using the Bayesian method with the same 
pre-specified threshold. The study will not stop for futility at the 
interim analysis. 
The detailed study operating characteristics and simulation 
results will be provided in the SAP. 
11.3.2 Interim/ 
Administrative 
Analyses 
There will be 2 interim analyses as described in the SAP. The 
Haybittle-Peto method is used to adjust the alpha-levels for the 
first interim, second interim, and final analyses to 0.0001, 
0.0001, and 0.025, respectively. The first interim analysis is an 
administrative interim analysis will be conducted when the first 
for regulatory agency review after 350 randomized subjects have 
completed 1-year follow-up visits. The second formal interim 
analysis will be carried out after enrollment in the randomized 
cohort is completed. This formal interim analysis will be 
conducted on the full N=1500 randomized subject cohort when a 
subset of the is planned to occur after 850 randomized subjects 
has completed 1-year follow-up (pending regulatory 
approval)visits. The piecewise exponential model30 based on 
outcomes among these subjects will be used to predict the 1-year 

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results by treatment group for the remaining enrolled subjects. 
The Bayesian method will be used to perform the hypothesis 
testing on the combined data sets. A final analysis will be 
performed on all subjects with completed 1-year data if non-
inferiority cannot be claimed at the formal interim analysis (see 
Section 11.1.1.3). Additional information may be found in the 
SAP. Additional analyses not defined in the protocol may also be 
conducted for regulatory agency review. 
11.3.3 Subgroup 
Analyses… 
Primary and pre-specified… as appropriate. 
In the 4D CT Imaging Substudy, computed tomography data will 
be analyzed after 200 subjects have reached 1-year follow-up.   
Section 25.2 
Definitions 
OPERA-
TIVE 
RISK 
Operative risk is determined…  
Low: Estimated 30-day risk of mortality is <3% 
Intermediate: Estimated 30-day risk… 
L 
08-Sep-2022 
90702637 
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Contact Information 
Beth Louh 
Senior Clinical Trial Manager… 
 
Sarah Zanon… 
Chemin de la Venoge 11 Ritterquai 8 
1024 Ecublens 4500 Solothurn, Switzerland 
Updated title 
 
 
Updated address 
Section 2, Synopsis 
Test Device and 
Sizes 
Addition of the ACURATE Prime Aortic Valve XL, ACURATE 
Prime Transfemoral Delivery System XL and ACURATE Prime 
Loading Kit XL. 
Addition of the 
ACURATE Prime 
XL Nested Registry; 
updated for clarity 
Device Name/Size 
Description 
ACURATE neo2™ 
Transfemoral Delivery 
System 
The delivery system is 
compatible with the S, 
M, and L all 3 valve 
sizes. 
Allows… access. 

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ACURATE Prime™ 
Aortic Valve XL 
Valve size: 
 
- XL (extra-large) 
with 29mm nominal 
diameter at waist level 
Includes 3 main components: 
-  A three-leaflet porcine pericardial 
bioprosthetic aortic valve. 
-  A self-expandable Nitinol stent. 
-  A double porcine pericardium skirt 
sutured on the inner and outer surface 
of the stent to prevent paravalvular 
leaks.  
Introduced via the iliofemoral artery. 
ACURATE Prime™ 
Transfemoral Delivery 
System XL 
Allows positioning and delivery of the 
transcatheter XL valve via iliofemoral access. 
ACURATE Prime™ 
Loading Kit XL 
Allows loading of the XL valve onto the 
delivery system.  
Section 2, Synopsis 
Study Design 
Study cohorts include the following: 
• 
ACURATE Prime™ XL Nested Registry: A non-
randomized, nested registry cohort of subjects who will 
receive the ACURATE Prime™ Transfemoral Aortic Valve 
System XL (ACURATE Prime XL Nested Registry). 
Participating centers will be a subset of United States 
centers that have enrolled subjects in ACURATE IDE. Data 
from subjects in this nested registry will be summarized 
separately from the randomized and Roll-In cohorts. 
ACURATE IDE Study Design Overview 
Updated figure to include the ACURATE Prime Nested Registry.   
Section 2, Synopsis 
Planned Number of 
Subjects… 
Subjects will be enrolled… up to 1670 1720 subjects total in the 
ACURATE IDE Roll-In and randomized cohorts and the 
ACURATE Prime XL Nested Registry as shown below. 
Cohort 
Number of Subjects 
ACURATE Prime XL 
Nested Registry 
50‡ 

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*  A subset... 
‡ Subjects will be enrolled at up to 20 centers in the United States. 
Section 2, Synopsis 
Method of 
Assigning … 
For the randomized cohort and Roll-In cohort, subjects will have a 
documented aortic annulus size of ≥21mm and ≤27mm based on 
pre-procedure diagnostic imaging. 
 
ACURATE Prime XL Nested Registry: Subjects will have a 
documented aortic annulus size of ≥26.5 mm and ≤29 mm based 
on pre-procedure diagnostic imaging. 
Section 2, Synopsis 
Follow-up Schedule 
The visits at 30 days, 6 months, 1 ̶ 5 years, 7 years, and 10 years 
are to be an office/clinical/in-person or telehealth visit… 
Add telehealth 
option 
Section 2, Synopsis 
Study Duration 
Enrollment is expected to be completed in approximately 36 
45 months; therefore, the total study duration is estimated to be 
approximately 1314 years. 
Updated estimate 
Section 2, Synopsis 
Inclusion Criteria 
IC2. Subject has… and ≤ 297 mm based… 
Allow for XL size 
valve 
Section 2, Synopsis 
Exclusion Criteria 
Vulnerable subjects (ISO 14155) will not be enrolled in 
ACURATE IDE. 
Per ISO 14155. 
Section 2, Synopsis 
Analysis Sets 
Among the Roll-In and ACURATE Prime XL cohorts, for the ITT 
analysis, all subjects… implanted. The Implanted analysis set will 
include all subjects who sign an Informed Consent Form and are 
implanted with an ACURATE valve. For these single-arm 
cohorts… 
Allow for XL size 
valve 
Section 2, Synopsis 
Sample Size 
Parameters for the 
Primary Endpoint 
Although the primary endpoint analysis is performed using the 
Bayesian method, the sample size calculation for the randomized 
cohort (see… 
Note 15: The… This formal interim analysis will be conducted on 
the full N=1500 randomized subject cohort after the first 1050a 
Updated for clarity 

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subset of the randomized subjects have completed 1-year follow-
up (pending regulatory approval). 
Section 2, Synopsis 
ACURATE Prime 
XL Nested Registry 
Statistical 
Hypothesis 
Mean aortic valve pressure gradient at 30 days post implant 
procedure is less than a performance goal (PG): 
H0: Gradient30D ≥ PG 
H1: Gradient30D < PG  
where Gradient30D is the 30-day mean aortic valve pressure 
gradient for the ACURATE Prime XL valve and PG is 15 mmHg. 
Addition of the 
ACURATE Prime 
XL Nested Registry 
 
Section 2, Synopsis 
Statistical Test 
Method for the 
ACURATE Prime 
XL Nested Registry  
A one-sample t-test will be used to test the one-sided hypothesis at 
a significance level of 2.5%. 
Section 2, Synopsis 
Sample Size 
Parameters for the 
ACURATE Prime 
XL Nested Registry 
• Expected 30-day mean pressure gradient from ACURATE 
Prime XL = 10 mmHgh 
• Expected standard deviation = 7 mmHg  
• PG = 15 mmHg 
• Test significance level (α) = 0.025 (1-sided) 
• Power > 90% 
• Evaluable number of subjects = Minimum of 40 subjects 
• Expected rate of attrition = 20% (8 subjects) 
• Planned enrollment of 50 subjects  
• The analysis population for the hypothesis testing will be the 
subject population implanted with the ACURATE Prime XL 
valve.    
h:  Based on Boston Scientific data on file and published data for 
large-annulus CoreValve devices: 

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Tang GHL, et al. Am J Cardiol 2019;124:1091-8 
Kalogeras K, et al. Catheter Cardiovasc Interv 2019;93:685-91 
Ussia GP, et al. EuroIntervention 2015;10:e1-e8 
Section 2, Synopsis 
Success Criteria for 
the ACURATE 
Prime XL Nested 
Registry 
If the P value from the one-sample t-test is < 0.025, the 
ACURATE Prime XL valve will be concluded to have a 30-day 
mean aortic valve pressure gradient < 15 mmHg. This corresponds 
to the one-sided upper 2.5% confidence bound of the observed 
30-day mean aortic valve pressure gradient being < 15 mmHg. 
Section 2, Synopsis 
Descriptive 
Statistics 
Descriptive statistics will be used to summarize data from subjects 
in the single-arm Roll-In and ACURATE Prime XL cohorts. 
Section 4.1.2 
Transcatheter Aortic 
Valve… 
Updated Table 4.1-1 with additional references regarding TAVR 
in large annuli: CoreValve – Large Annuli (2015)43; UK & Ireland 
Implanters’ Registry (2019)47; EVOLUT R – Large Annuli 
(2019)48; TVT Registry – Large Annulus (2019)49 
Section 4.2 Study 
Rationale 
The ACURATE device… limit PVR. The subsequent ACURATE 
neo2 and ACURATE Prime Transfemoral Valve Systems 
waswere designed… 
Section 5.1 
ACURATE 
Transfemoral Aortic 
Valve System (Test) 
• A single use aortic valve, the ACURATE neo2™ Aortic Valve 
(valve sizes S, M, and L) or the ACURATE Prime™ Aortic 
Valve (valve size XL)  
• A single use transfemoral delivery system, the ACURATE 
neo2™ Transfemoral Delivery System (for use with valve sizes 
S, M, and L) or the ACURATE Prime Transfemoral Delivery 
System (for use with valve size XL) 
• A single use loading kit, ACURATE Prime™ Loading Kit XL 
(to allow loading of the XL valve onto the delivery system) 

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Note: The single use ACURATE neo2™ Loading Kit is packaged 
with the ACURATE neo2™ Transfemoral Delivery System. 
Valves and the delivery system are manufactured in Belo 
Horizonte, Brazil. Delivery systems and loading kits are 
manufactured in Ecublens, Switzerland and/or Galway, Ireland. 
All components are investigational and are labeled as such. The 
device components are described briefly below. Additional 
information is provided in the ACURATE neo and ACURATE 
Prime Clinical Directions/Instructions for Use (DFU/IFU) and the 
IB. 
Note: Throughout this document DFU and IFU are used 
interchangeably. 
Section 5.1.1. 
ACURATE neo2™ 
Aortic Valve and 
ACURATE Prime™ 
Aortic Valve XL 
The ACURATE neo2 Aortic Valve is an iteration of the CE Mark-
approved ACURATE neo™ Aortic Bioprosthesis (Boston 
Scientific Corporation, Marlborough, MA, USA). The 
ACURATE Prime Aortic Valve XL is an iteration of the CE 
Mark-approved ACURATE neo2 Aortic Valve. There are 3 valve 
sizes of ACURATE neo2 (Small, Medium, and Large) intended 
for a native annulus diameter range between 21 mm and 27 mm 
and 1 valve size of ACURATE Prime (Extra Large) intended for a 
native annulus diameter range between 26.5 mm and 29 mm as 
shown in Table 5.1-1. 
Added rows to Table 5.1-1 ACURATE neo2 and ACURATE 
Prime Aortic Valve Size Chart 
Extra Large 
(XL) 
29mm 
26.5 mm < native annulus diameter ≤ 29 mm 
a: ACURATE neo2™ available in sizes S, M, L and ACURATE Prime™ 
available in size XL 
 

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The valves are shown in Figure 5.1-1 (ACURATE neo2 Aortic 
Valve in Panel A and ACURATE Prime Aortic Valve XL in Panel 
B). Each valve consists of… 
…intended to limit further the extent of PVR. The ACURATE 
Prime Aortic Valve XL iteration allows easier removal of a fully 
loaded valve and has optimized radial force with the addition of 
connected links. The valve… 
 
UPDATED Figure 5.1-1 with addition of a picture of the 
ACURATE Prime Aortic Valve XL (Panel B). 
Section 5.1.2. 
ACURATE neo2™ 
Transfemoral 
Delivery System 
and ACURATE 
Prime Transfemoral 
Delivery System XL 
The ACURATE neo2 Transfemoral Delivery System and 
ACURATE Prime Transfemoral Delivery System XL are is 
transfemoral delivery systems for the guidance and placement of 
the valve implant.  
ACURATE neo2 is a slightly… 
The ACURATE Prime Transfemoral Delivery System XL is a 
slightly modified version of the ACURATE neo2 Transfemoral 
Delivery System. The system is compatible with the 14F 
iSLEEVE introducer (see Section 5.1.3 below) and has a new 
distal release mechanism to allow quicker final valve release and 
improved Figure 5.1 5 shows an overview of the system and 
Figure 5.1 6 shows a close-up of the distal end. Prior to use, the 
ACURATE Prime Aortic Valve XL is loaded onto the delivery 
system with the investigational ACURATE Prime Loading Kit 
XL.  
ADDED Figure 5.1-5 and Figure 5.1-6 
The delivery systems are single-use catheters. Please see 
Section 10.7.2.2 for additional information on preparing and using 
the investigational devices… 
Only BSC authorized and trained personnel may load the 
ACURATE Valve. 

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Section 5.1.3 
Introducer Set 
Only the iSLEEVE shall be used with the ACURATE Prime 
Transfemoral Delivery System XL.  
Section 5.3.1 Test 
Device 
The study Manual of Operations includes the DFU/IFU for the 
ACURATE neo2 Valve, and the ACURATE neo2 Transfemoral 
Delivery System, ACURATE Prime Aortic Valve, ACURATE 
Prime Transfemoral Delivery System, and ACURATE Prime 
Loading Kit. 
Addition of the 
ACURATE Prime 
XL Nested Registry; 
updated for clarity 
 
Section 6.2 Study 
Endpoints 
Among the Roll-In and ACURATE Prime XL cohorts of 
ACURATE IDE, all subjects… 
Section 7.1 Scale… 
Subjects… There will be up to 1670 1720 subjects total in… 
The ACURATE IDE study cohorts… 
• ACURATE Prime™ XL Nested Registry: A non-
randomized, nested registry cohort of subjects who will receive 
the ACURATE Prime™ Transfemoral Aortic Valve System 
XL (ACURATE Prime XL Nested Registry). Participating 
centers will be a subset of United States centers that have 
enrolled subjects in ACURATE IDE. Data from subjects in this 
nested registry will be summarized separately from the 
randomized and Roll-In cohorts. There will be 50 subjects at 
centers in the United States enrolled in this registry. 
All subjects implanted… Enrollment is expected to be completed 
in approximately 36 45 months; therefore, the total study duration 
is estimated to be approximately 13 14 years. 
UPDATED Figure 7.1-1 to include the ACURATE Prime Nested 
Registry. 
Section 7.2 
Treatment 
Assignment 
Subjects in the non-randomized, nested registry cohort will all 
receive ACURATE Prime™ Transfemoral Aortic Valve System 
XL valves. 

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UPDATED Table 7.2-1 to reflect addition of ACURATE Prime 
XL valve, delivery system, and loading kit. 
Note 2: Subjects in the Roll-In (Section 9.1.1) and randomized 
(Section 9.1.2) cohorts will have a documented aortic annulus size 
of ≥21mm and ≤27mm based on pre-procedure diagnostic 
imaging. Subjects in the ACURATE Prime XL Nested Registry 
(Section 9.1.3) will have a documented aortic annulus size of 
≥26.5mm and ≤29mm based on pre-procedure diagnostic imaging. 
Section 7.3 
Justification for the 
Study Design 
There will be up to 1670 1720 subjects total in ACURATE IDE. 
In order …do 2 Roll-In cases each), and1500 subjects will be 
randomized and enrolled, and 50 subjects will be enrolled in the 
ACURATE Prime XL Nested Registry. 
Section 8.2 
Inclusion Criteria 
Table 8.2-1: Updated IC2: …annulus size of ≥21 mm and 
≤297 mm  
Section 8.3 
Exclusion Criteria 
…clinical study. No vulnerable populations will be enrolled in this 
study. See Section 25.2 for the definition of a vulnerable subject.   
Updated per 
ISO 14155 
Section 9.1.3 
ACURATE Prime 
XL Nested Registry 
For the ACURATE Prime XL Nested Registry, subjects confirmed 
eligible for the study by the CRC (see Section 21.2) and who 
provided written informed consent (see Section 20) are considered 
enrolled in the study as soon as an attempt is made to insert the 
test device into the subject’s femoral artery. 
Addition of the 
ACURATE Prime 
XL Nested Registry 
 
Section 9.5 End-of-
Study Definition 
Visits at 30 days, 6 months, 1–5 years, 7 years and 10 years are 
office/clinical/in-person or telehealth visits. 
Allow for telehealth 
Section 10.1 Data 
Collection 
All subjects... Physical Office/clinical/ visits/or in-person or 
telehealth follow-up visits… 
Note: All required ECG measurements and transthoracic 
echocardiography measurements must be done for all subjects 
who have a transcatheter valve implanted in the aortic position 
during the index procedure, even if the associated follow-up 
assessment is carried out via telehealth. 
Allow for telehealth; 
add ACURATE 
Prime XL Registry 

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Table 10.1-1: Added “Telehealth” to column header and “Visits at 
30 days, 6 months, 1–5 years, 7 years and 10 years are 
office/clinical/in-person or telehealth visits; all required ECG 
measurements and TTE measurements must be done for all 
subjects who have a transcatheter valve implanted in the aortic 
position during the index procedure, even if the associated follow-
up assessment is carried out via telehealth.”  
 
UPDATED Figure 10.1-1 to show addition of ACURATE Prime 
XL Registry  
Section 10.7.2 
ACURATE 
Transfemoral… 
Only the iSLEEVE introducer shall be used with the ACURATE 
Prime Transfemoral Delivery System XL (see Section 5.1.3). 
Addition of 
ACURATE Prime 
XL Registry 
 
 
Section 10.7.2.2 
Preparing… 
The appropriate DFU… A similar procedure is used for 
preparation of the ACURATE Prime Aortic Valve XL; please see 
the corresponding DFU/IFU and other training material provided 
by BSC. 
• Device size (Small, Medium, or Large, or Extra Large) 
Figure 10.7-1: Note: This example shows the ACURATE neo2 
valve. 
Section 10.10 
Follow-up 
Note 2: Where indicated in Table 10.1-1, the follow-up visits must 
be conducted in-person or as telehealth visits. If an in-
person/telehealth assessment cannot be performed, follow-up by 
telephone call should be attempted. The subject or the subject’s 
physician should provide rationale for why the subject cannot 
come in for comply with the follow-up in-person/telehealth 
assessment visit.  
Allow for telehealth 
Section 10.10.1  
30-day Follow-up 
All enrolled subjects must be evaluated 30 (±7) days after the 
index procedure in person or via telehealth. During… 

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Note 1:  A 12-lead ECG must be obtained for all subjects, even if 
the associated follow-up assessment is carried out via telehealth. 
Note 2: TTE must be done for all subjects who have a 
transcatheter valve implanted in the aortic position during the 
index procedure, even if the associated follow-up assessment is 
carried out via telehealth. 
Section 10.10.2 
6-month Follow-up 
All enrolled subjects must be evaluated 180 (±30) days after the 
index procedure in person or via telehealth. During… 
Note 1:  A 12-lead ECG must be obtained for all subjects, even if 
the associated follow-up assessment is carried out via telehealth. 
Note 2: TTE must be done for all subjects who have a 
transcatheter valve implanted in the aortic position during the 
index procedure, even if the associated follow-up assessment is 
carried out via telehealth. 
Section 10.10.3  
1-year Follow-up 
All enrolled subjects must be evaluated 30 (±7) days after the 
index procedure in person or via telehealth. During… 
Note 1:  A 12-lead ECG must be obtained for all subjects, even if 
the associated follow-up assessment is carried out via telehealth. 
Note 2: TTE must be done for all subjects who have a 
transcatheter valve implanted in the aortic position during the 
index procedure, even if the associated follow-up assessment is 
carried out via telehealth. 
Section 10.10.4 
Annual Follow-up… 
All implanted subjects must be evaluated in person or by 
telehealth visit at 2… 
 
Note: TTE must be done for all subjects who have a transcatheter 
valve implanted in the aortic position during the index procedure, 
even if the associated follow-up assessment is carried out via 
telehealth. 

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Section 10.10.5 
Follow-up (±60 
Days) at 7 and 10… 
All implanted subjects must be evaluated in person or via 
telehealth at 7 and… 
 
Note: TTE must be done for all subjects who have a transcatheter 
valve implanted in the aortic position during the index procedure, 
even if the associated follow-up assessment is carried out via 
telehealth. 
Section 10.10.11 
Study Completion 
Visits in the first 5 years and at 7 and 10 years are office or /in-
person/telehealth visits. 
 
Visits in the first 5 years and at 7 and 10 years are office/in-
person/telehealth visits. 
Section 11.1 
Endpoints 
Data will be summarized separately for the specific statistical 
hypothesis associated with the ACURATE Prime™ XL Nested 
Registry. Descriptive statistics also will be used to summarize data 
from subjects in the single-arm ACURATE Prime XL cohort. 
Statistical 
hypothesis for the 
ACURATE Prime 
XL Nested Registry. 
Section 11.1.1.2 
Sample Size… 
Note 5: The administrative... after the first 1050 a subset of the 
randomized subjects have completed 1-year follow-up (pending 
regulatory approval). The… 
Updated for clarity 
Section 11.1.2 
ACURATE Prime 
XL Nested Registry 
Statistical 
Assessment 
The statistical assessment for the ACURATE Prime XL Nested 
Registry is summarized in the sections below. Additional 
information may be found in the SAP. 
11.1.2.1 Statistical Hypothesis – ACURATE Prime XL Nested 
Registry 
The statistical hypothesis is that the mean aortic valve pressure 
gradient at 30 days post implant procedure is less than a 
performance goal (PG): 
 
H0: Gradient30D ≥ PG 
 
H1: Gradient30D < PG 
Statistical 
hypothesis for the 
ACURATE Prime 
XL Nested Registry. 

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where Gradient30D is the 30-day mean aortic valve pressure 
gradient for the ACURATE Prime XL valve and PG is 15 mmHg. 
A one-sample t-test will be used to test the one-sided hypothesis at 
a significance level of 2.5%. 
11.1.2.2 Sample Size Parameters for the ACURATE Prime XL 
Nested Registry  
The sample size calculation is based on the following 
assumptions. 
• Expected 30-day mean pressure gradient from ACURATE 
Prime XL = 10 mmHg 
• Expected standard deviation = 7 mmHg  
• PG = 15 mmHg 
• Test significance level (α) = 0.025 (1-sided) 
• Power > 90% 
• Evaluable number of subjects = Minimum of 40 subjects 
• Expected rate of attrition = 20% (8 subjects) 
• Planned enrollment of 50 subjects  
• The analysis population for the hypothesis testing will be the 
subject population implanted with the ACURATE Prime XL 
valve.   
Note: The expected mean gradient is based on Boston Scientific 
data on file and published data for large-annulus CoreValve 
devices43.48.49.  
11.1.2.3 Success Criteria for the ACURATE Prime XL Nested 
Registry  
If the P value from the one-sample t-test is < 0.025, the 
ACURATE Prime XL valve will be concluded to have a 30-day 

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mean aortic valve pressure gradient < 15 mmHg. This corresponds 
to the one-sided upper 2.5% confidence bound of the observed 
30-day mean aortic valve pressure gradient being < 15 mmHg. 
11.1.3 Baseline 
Comparability 
Baseline data will be summarized by treatment group for the 
randomized subjects and separately for the Roll-In and 
ACURATE Prime XL Nested Registry subjects. 
 
Please see Section 11.1.2 regarding statistical testing for the 
ACURATE Prime XL Nested Registry. 
Statistics for 
ACURATE Prime 
XL Nested Registry 
 
11.1.4 Post-
procedure… 
Please see Section 11.1.2 regarding statistical testing for the 
ACURATE Prime XL Nested Registry. 
11.2.1 Analysis Sets 
Subjects in the randomized cohort are considered enrolled in the 
study upon randomization. Among the randomized… 
 
…With the Roll-In and ACURATE Prime™ XL Nested Registry 
cohorts, the subject is considered enrolled in the trial when there is 
an attempt made to insert the ACURATE Transfemoral Aortic 
Valve System into the subject’s femoral artery. 
 
… The implanted population includes all subjects who sign an ICF 
and are implanted with the an ACURATE valve. 
Updated for clarity 
 
 
Statistics for 
ACURATE Prime 
XL Nested Registry 
 
 
Updated for clarity 
 
11.2.5 Reporting 
Events 
For all subjects in the ACURATE IDE Roll-In and ACURATE 
Prime™ XL Nested Registry cohort, all events that occur from the 
time of enrollment will be reported. 
Statistics for 
ACURATE Prime 
XL Nested Registry 
11.3.2 Interim/ 
Administrative 
Analyses 
This formal interim analysis will be conducted on the full N=1500 
randomized subject cohort after the first 1050a subset of the 
randomized subjects have completed 1-year follow-up (pending 
regulatory approval). 
Updated for clarity 
11.3.3 Subgroup 
Analyses for 
Added 2 subgroups: 
• Valve size (Small, Medium, Large)  
Gain additional 
information on 

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Randomized 
Subjects 
• Operative risk (low, intermediate, high/extreme)  
 
outcomes in other 
subgroups 
16.2 Investigator 
Responsibilities 
• Ensure that, if appropriate… participation in the clinical 
investigation (e.g., implant card) …  
Added for clarity 
16.4.2 Training with 
the Investigational 
Device 
The ACURATE neo2 Transfemoral Aortic Valve System 
Healthcare Personnel (HCP) Training Plan developed for this 
study meets the requirements of ISO 5840-3 and includes the 
following elements.  
 
Note 3: Centers selected to participate in the ACURATE Prime 
XL Nested Registry will receive additional training on the 
ACURATE Prime investigational device. An experienced BSC 
representative will provide technical support as needed during 
valve preparation and implantation. 
Updated name of the 
training plan 
 
 
 
Addition of 
ACURATE Prime 
XL Nested Registry 
Section 25.2 
Definitions 
VULNERABLE 
SUBJECTS 
(per ISO 14155) 
Individuals who are unable to fully 
understand all aspects of the investigation 
that are relevant to the decision to 
participate, or who could be manipulated 
or unduly influenced as a result of a 
compromised position, expectation of 
benefits or fear of retaliatory response 
Updated to comply 
with ISO 14155 
M 
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Section 2, Synopsis, 
Test Device and 
Sizes 
Added * to ACURATE Prime™ in the size table. 
* ACURATE Prime XL is only available in the United States. 
Added for clarity 
Section 2, Synopsis, 
Control Device and 
Sizes 
In the Main Randomized Cohort and in the Extended Durability 
Study (see study cohorts described below), subjects… 
 
Note 1: Every subject in the Main Randomized Cohort and the 
Extended Durability Study must be deemed… 

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Section 2, Synopsis, 
Study Design 
• Main Randomized Cohort… 
• Roll-In Cohort: …at least 2 Roll-In cases with ACURATE neo2 
before… 
• 4D CT Imaging Substudy: …will include subjects from the 
Main Randomized Cohort in a… 
• ACURATE Prime XL Nested Registry: A nonrandomized… 
separately from the randomized and Roll-In other cohorts. 
• ACURATE Extended Durability Study: An additional 1:1 
randomized study (ACURATE versus Control [commercially 
available SAPIEN 3 or CoreValve] TAVR device) including only 
subjects considered to be at low surgical risk. Subjects will receive 
ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime 
XL. Randomization will be stratified by center and by intended 
control device. Low-risk subjects receiving ACURATE neo2 will 
be enrolled in the Extended Durability Study only after enrollment 
of the Main Randomized Cohort is completed. Enrollment of low-
risk subjects with ACURATE Prime XL will start after enrollment 
in both the ACURATE Prime XL Nested Registry and the Main 
Randomized Cohort is completed. Data from subjects in the 
Extended Durability Study will be summarized separately from 
other cohorts. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in the ACURATE Extended 
Durability Study. 
 
• ACURATE Continued Access Study (CAS): An additional 
cohort of subjects receiving ACURATE neo2 (S, M, and L valve 
sizes) or ACURATE Prime XL. Enrollment of subjects with 
ACURATE neo2 will start after enrollment of the ACURATE IDE 
Main Randomized Cohort is completed. Enrollment of subjects 
with ACURATE Prime XL will start after enrollment in both the 
ACURATE Prime XL Nested Registry and Main Randomized 
Added for clarity 
and to include the 
Extended Durability 
Study and the 
Continued Access 
Study 

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Cohort is completed. Subjects at all surgical risks may be enrolled 
in ACURATE CAS, but low-risk subjects will be considered for 
enrollment only after enrollment in the Extended Durability Study 
is completed. Data from subjects in the ACURATE CAS will be 
summarized separately from other cohorts and will be used to 
further assess performance and safety. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE CAS. 
 
The devices and risk levels for the ACURATE IDE cohorts are 
summarized in the table below. 
 
Added a table showing “Devices And Risk Levels for the 
ACURATE IDE Cohorts.” 
 
Updated ACURATE IDE Study Design Overview figure 

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Section 2, Synopsis, 
Planned Number of 
Subjects… 
Subjects… Europe. In total, there will be up to 1720 2820 subjects 
total enrolled in the ACURATE IDE roll-in and randomized 
across the various cohorts and the ACURATE Prime XL Nested 
Registry as shown below. It is expected that >80% of enrolled 
subjects will be from the United States. The number of subjects 
intended for each cohort is shown in the table below. 
 
Cohort 
Number of 
Subjects 
Main Randomized Cohort 
1500* 
Roll-In Cohort 
Up to 170 
ACURATE Prime XL Nested Registry 
50‡ 
ACURATE Extended Durability Study 
A minimum of 
100† 
ACURATE Continued Access Study (CAS) 
Up to 1000§ 
*  A subset of subjects (minimum of 200) in the Main 
Randomized Cohort will also be enrolled in the 4D CT 
Imaging Substudy. 
‡  Subjects will be enrolled at up to 20 centers in the United 
States. 
† Only low-risk subjects will be included in the Extended 
Durability Study. 
§ Low-risk subjects will be considered for enrollment in 
ACURATE CAS after enrollment is completed in the Extended 
Durability Study. 
 
Section 2, Synopsis, 
Method of 
Assigning… 
Main Randomized Cohort: A computer… 
 
ACURATE Extended Durability Study: A computer generated 
list of random treatment allocations (randomization schedule) will 
be used to assign subjects to treatment in a 1:1 ratio of ACURATE 
to Control. Only subjects considered to be at low surgical risk will 
Added for the 
additional cohorts. 
Annulus size 
updated for the 
additional cohorts 
for better valve 

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be included in this cohort. Randomization will be stratified by 
center and by intended control device. Subjects will receive 
ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime 
XL. Subjects with a documented aortic annulus size of ≥20.5mm 
and ≤27 mm may be enrolled in the Extended Durability Study 
after enrollment is concluded in the Main Randomized Cohort. 
Subjects with a documented aortic annulus size of ≥26.5mm and 
≤29mm may be enrolled in the Extended Durability Study after 
enrollment is concluded in both the Main Randomized Cohort and 
the ACURATE Prime XL Nested Registry.  
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in the ACURATE Extended 
Durability Study. 
 
ACURATE Continued Access Study: Subjects will receive 
ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime 
XL. Subjects with a documented aortic annulus size of ≥20.5mm 
and ≤27mm may be enrolled in ACURATE CAS after enrollment 
is concluded in the Main Randomized Cohort. Subjects with a 
documented aortic annulus size of ≥26.5mm and ≤29mm may be 
enrolled in ACURATE CAS after enrollment is concluded in both 
the Main Randomized Cohort and the ACURATE Prime XL 
Nested Registry. Subjects at all surgical risk levels may be 
enrolled in ACURATE CAS but low-risk subjects will be 
considered for enrollment only after enrollment is completed in 
the Extended Durability Study. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE CAS. 
sizing based on 
operator experience. 
Section 2, Synopsis, 
Follow-up Schedule 
The visits… or telehealth (https/telehealth.HHS.gov) visit… 
Added for clarity 

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Section 2, Synopsis, 
Study Duration 
…Enrollment is expected to be completed in approximately 45 62 
months; therefore, the total study duration is estimated to be 
approximately 14 16 years. 
Added for the 
additional cohorts. 
Section 2, Synopsis, 
Inclusion Criteria 
IC2. Subject… size of ≥21 20.5 mm… and, for the Main 
Randomized Cohort and Extended Durability Study, is deemed… 
Annulus size 
updated for the 
additional cohorts 
for better valve 
sizing based on 
operator experience. 
Section 2, Synopsis, 
Statistical Methods, 
Analysis Sets 
Analysis sets for the ACURATE IDE Main Randomized Cohort, 
and the Extended Durability Study are listed below. Subjects in 
the Main Randomized Cohort and the Extended Durability Study 
are considered… 
Note 11: For the Implanted Main Randomized Cohort and 
Extended Durability Study analysis set, if a subject… 
Among the Roll-In, and ACURATE Prime XL, and Continued 
Access Study cohorts, for… 
Added for clarity 
and to include the 
Extended Durability 
Study and the 
Continued Access 
Study 
Section 2, Synopsis, 
Statistical Methods, 
Primary Endpoint 
In the Main Randomized Cohort, the primary endpoint… 
Section 2, Synopsis, 
Statistical Methods, 
Statistical Test 
Method for the 
Primary Endpoint 
For the Main Randomized Cohort, the statistical hypothesis… 
Section 2, Synopsis, 
Sample Size 
Parameters for the 
Primary Endpoint 
Note 15: The administrative… the first 350 randomized subjects 
in the Main Randomized Cohort have completed… The formal 
interim… enrollment in the Main Randomized Cohort is 
completed. This formal interim analysis will be conducted on the 
full N=1500 randomized subject cohort of the Main Randomized 

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Cohort after the first 1050 randomized subjects in the Main 
Randomized Cohort have completed… 
Section 2, Synopsis, 
Success Criteria for 
the Primary 
Endpoint 
The Bayesian method is used to test the non-inferiority hypothesis 
of the primary endpoint on the Main Randomized Cohort. To 
establish… 
Section 2, Synopsis, 
Statistical Methods, 
Descriptive 
Statistics Summary 
Data will be summarized separately for each cohort. In addition to 
the hypothesis tests listed above, descriptive statistics will be used 
to summarize data from subjects in the single-arm Roll-Inand 
ACURATE Prime XL cohorts. Full methods will be described in 
the statistical analysis plan. 
Updated for clarity 
Section 5.1.1 
ACURATE neo2 
Aortic Valve and 
ACURATE Prime 
Aortic Valve XL 
There are 3 valve sizes of ACURATE neo2 (Small, Medium, and 
Large) intended for a native annulus diameter range between 21 
mm and 27 mm and 1 valve size of ACURATE Prime (Extra 
Large). intended for a native annulus diameter range between 26.5 
mm and 29 mm as shown in Table 5.1-1 shows the sizing chart 
used for the ACURATE IDE Roll-In Cohort, Main Randomized 
Cohort, and ACURATE Prime XL Nested Registry. Table 5.1-2 
shows the sizing chart used for the Extended Durability Study and 
the Continued Access Study. Please see Section 7.1 below for 
study cohort descriptions. 
Note: ACURATE Prime™ XL is only available in the United 
States. 
Table 5.1-1: ACURATE neo2 and ACURATE Prime Aortic 
Valve Size Chart – Main Randomized Cohort, Roll-In Cohort and 
ACURATE Prime XL Nested Registry 
Added superscript b to Extra Large (XL) in the size table. 
b: ACURATE Prime XL is only available in the United States. 
 
Added for the 
additional cohorts. 
Annulus size 
updated for the 
additional cohorts 
for better valve 
sizing based on 
operator experience.  

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Table 5.1-2: ACURATE neo2 and ACURATE Prime Aortic 
Valve Size Chart – Extended Durability Study and Continued 
Access Study [Added table] 
Section 5.1.3 
Introducer Set 
It is recommended that the commercially available Lotus 
Introducer Set (size Small [LIS S]; manufactured by Creganna-
Tactx Medical and distributed by Boston Scientific Corporation, 
Marlborough, MA, USA) or The commercially available 14F 
iSLEEVE™ Introducer Set (iSLEEVE; Boston Scientific 
Corporation, Marlborough, MA, USA) shall be used as an 
accessory to the ACURATE neo2 Transfemoral Aortic Valve 
System and the ACURATE Prime Transfemoral Aortic Valve 
System during the procedure. Only The iSLEEVE shall be used 
with the ACURATE Prime Transfemoral Delivery System XL. 
Both introducers areis composed of a dilator and an introducer 
sheath manufactured with materials commonly used in medical 
devices having contact with circulating blood. Both introducers It 
has ve a … introduction. The LIS S is suitable for use in subjects 
with femoral vascular access ≥6.0 mm. The 14F iSLEEVE... 
Note: In countries where the iSLEEVE and LIS-S areis approved, 
the commercial device will be used. They It will be considered an 
investigational devices in countries where they are it is not 
approved. 
Lotus Introducer Set 
is no longer on the 
market 
Section 5.2 Control 
Device 
The control device… native annulus range between 2120.5mm 
and 2729mm 
 
Note: Every subject in the Main Randomized Cohort and the 
Extended Durability Study must… 
Updated for the 
Extended Durability 
study 
Section 6.2 Study 
Endpoints 
Outcomes in the randomized cohorts of the ACURATE IDE trial 
(Main Randomized Cohort and Extended Durability Study) will… 
Among the Roll-In, and ACURATE Prime XL, and CAS 
cohorts… 
Added due to 
inclusion of the 
Extended Durability 
Study and the 

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Section 6.3 Primary 
Endpoint 
The primary endpoint… The primary analysis set for the primary 
endpoint for the Main Randomized Cohort is the ITT… 
Continued Access 
Study and updated 
for clarity 
Section 7.1 Scale 
and Duration 
Subjects will be enrolled… up to 17202380 subjects total… To 
achieve sufficient distribution of lower risk subjects in the Main 
Randomized Cohort, there… 
 
• ACURATE Extended Durability Study: An additional 1:1 
randomized study (ACURATE versus Control [commercially 
available SAPIEN 3 or CoreValve] TAVR device) including only 
subjects considered to be at low surgical risk. Randomization will 
be stratified by center and by intended control device. Low-risk 
subjects receiving ACURATE neo2 will be enrolled in the 
Extended Durability Study only after enrollment of the Main 
Randomized Cohort is completed. Enrollment of low-risk subjects 
with ACURATE Prime XL will start after enrollment in both the 
Main Randomized Cohort and the ACURATE Prime XL Nested 
Registry is completed. Data from subjects in the Extended 
Durability Study will be summarized separately from other 
cohorts. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE Extended 
Durability Study. 
 
• ACURATE Continued Access Study (CAS): An additional 
cohort of subjects receiving ACURATE neo2 (S, M, and L valve 
sizes) or ACURATE Prime XL. Enrollment of subjects with 
ACURATE neo2 will start after enrollment of the ACURATE IDE 
Main Randomized Cohort is completed. Enrollment of subjects 
with ACURATE Prime XL will start after enrollment in both the 
Main Randomized Cohort and the ACURATE Prime XL Nested 
Registry is completed. Subjects at all surgical risks may be 

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enrolled in ACURATE CAS, but low-risk subjects will be 
considered for enrollment only after enrollment in the Extended 
Durability Study is completed. Data from subjects in ACURATE 
CAS will be summarized separately from other cohorts and will be 
used to further assess performance and safety. 
Note: Centers must complete the roll-in phase of the study, if 
applicable, before participating in ACURATE CAS. 
 
The devices to be used and the subject risk levels for the 
ACURATE IDE cohorts are summarized below in Table7.1-1. 
 
Added new Table 7.1-1: Risk Levels and Devices for 
ACURATE IDE Cohorts 
 
All subjects implanted… be completed in approximately 45 62 
months; therefore, the total study duration is estimated to be 
approximately 14 16 years… 
 
The study design is summarized below in Figure 7.1-1. As noted 
above, enrollment in the Extended Durability Study will 
commence for low-risk subjects receiving ACURATE neo2 after 
enrollment of the Main Randomized Cohort is completed. 
Enrollment of low-risk subjects receiving ACURATE neo2 in 
ACURATE CAS will begin after enrollment in the Extended 
Durability Study is completed. Enrollment of low-risk subjects 
with ACURATE Prime XL will start after enrollment in both the 
Main Randomized Cohort and the ACURATE Prime XL Nested 
Registry is completed. 
 
Updated Figure 7.1-1 ACURATE IDE Study Design. 

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Section 7.2 
Treatment 
Assignment 
For the randomized cohorts (Main Randomized Cohort and 
Extended Durability Cohort), eligible subjects… 
 
Subjects in the non-randomized ACURATE Prime XL Nested 
Registry cohort will all receive ACURATE Prime™ Transfemoral 
Aortic Valve System XL valves. Subjects in the non-randomized 
ACURATE CAS will receive ACURATE neo2 or ACURATE 
Prime XL valves. 
 
Note 2: Subjects in the Roll-In cohort (Section 9.1.1) and Main 
Randomized Cohort (Section 9.1.2) will have a documented aortic 
annulus size of ≥21mm and ≤27mm based on pre-procedure 
diagnostic imaging (see Table 5.1-1). Subjects in the ACURATE 
Prime XL Nested Registry (Section 9.1.3) will have a documented 
aortic annulus size of ≥26.5mm and ≤29mm based on pre-
procedure diagnostic imaging (see Table 5.1-1). Subjects in the 
Extended Durability Study (Section 9.1.4) and the Continued 
Access Study (Section 9.1.5) will have a documented aortic 
annulus size of ≥20.5mm and ≤29mm based on pre-procedure 
diagnostic imaging (see Table 5.1-2). 
Section 7.3 
Justification for the 
Study Design 
There will be up to 1720 2820 subjects total in ACURATE IDE… 
In order to support… and enrolled in the Main Randomized 
Cohort, and 50 subjects will be enrolled in the ACURATE Prime 
XL Nested Registry at a subset of U.S. centers, a minimum of 100 
subjects will be randomized in the Extended Durability Study, and 
up to 1000 subjects will be enrolled in the ACURATE Continued 
Access Study… and ≥ 35% low risk subjects enrolled in the Main 
Randomized Cohort. 
Section 8.2 
Inclusion Criteria 
Table 8.2-1 ACURATE IDE Inclusion Criteria 
IC2. Subject… size of ≥21 20.5 mm… and, for the Main 
Randomized Cohort and Extended Durability Study, is deemed… 

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Section 9.1.2 Main 
Randomized Cohort 
Subjects 
For the Main Randomized Cohort, subjects… 
Section 9.1.4 
ACURATE 
Extended Durability 
Study Subjects 
Subjects confirmed eligible for the ACURATE Extended 
Durability Study by the CRC (see Section 21.2) and who provided 
written informed consent (see Section 20) are considered enrolled 
in the study upon randomization. 
Section 9.1.5 
ACURATE 
Continued Access 
Study Subjects 
For the ACURATE Continued Access Study, subjects confirmed 
eligible for the study by the CRC (see Section 21.2) and who 
provided written informed consent (see Section 20) are considered 
enrolled in the study as soon as an attempt is made to insert the 
test device into the subject’s femoral artery. 
Section 10.1 Data 
Collection 
All subjects… Office/clinical/in-person or telehealth 
(https/telehealth.hhs.gov) follow-up… 
Table 10.1-1: Updated note r to clarify that after 5 years adverse 
events should be collected for both the test and control devices. 
Updated Figure 10.1 1: Data Collection Schedule for 
ACURATE IDE 
Section 10.3 
Informed Consent 
Note: Centers may use remote consent as allowed by institutional 
policy and the center’s IRB/REB/HREC/IEC. 
Updated for clarity 
Section 10.7.2 
ACURATE 
Transfemoral… 
The DFUs/IFUs for the ACURATE Transfemoral Aortic Valve 
System should be followed. The commercially available 14F 
iSLEEVEA compatible introducer sheath (see Section 5.1.3) 
shouldshall be prepared and placed in the subject’s femoral artery 
as per the introducer DFU/IFU. The commercially available LIS S 
introducer or the commercially available 14F iSLEEVE introducer 
are is recommended for the ACURATE neo2 Transfemoral Aortic 
Valve System. Only the iSLEEVE introducer shall be used with 
the ACURATE Prime Transfemoral Delivery System XL (see 
Section 5.1.3). 
Lotus Introducer Set 
is no longer on the 
market. The 
iSLEEVE has been 
fully tested with 
ACURATE neo2 
and ACURATE 
Prime. 

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 11 
Statistical 
Considerations 
Full methods are described in the statistical analysis plan. 
Updated for clarity 
Section 11.1 
Statistical 
Considerations, 
Endpoints 
The randomized data from the Main Randomized Cohort of the 
ACURATE IDE trial… 
 
Data will be summarized separately for subjects in the ACURATE 
Extended Durability Study. Descriptive statistics will be used to 
summarize these data and no statistical inference will be made. 
 
Data will be summarized separately for subjects in the single-arm 
ACURATE Continued Access Study. Descriptive statistics will be 
used to summarize these data and no statistical inference will be 
made. 
Updated for clarity 
and added due to 
inclusion of the 
Extended Durability 
Study and the 
Continued Access 
Study 
Section 11.1.1.2 
Sample Size 
Parameters for the 
Primary Endpoint – 
Main Randomized 
Cohort 
• Analyses: One administrative, one formal interim, one final (see 
Note 5 and Note 6 below) 
Note 3:  The estimated proportions of subjects in the Main 
Randomized Cohort by operative risk level isare 10%... 
Note 5:  The administrative… first 350 Main Randomized Cohort 
subjects… after enrollment in the Main Randomized Cohort is 
completed. This formal interim analysis will be conducted on the 
full N=1500 randomized subject cohort of the Main Randomized 
Cohort after the first 1050 randomized subjects in the Main 
Randomized Cohort have completed… 
Note 6: Analyses of the Extended Durability Study and the 
ACURATE CAS are not expected to occur when the formal 
interim analysis is performed on the Main Randomized Cohort. 
See Section 11.1.2 below for information on analyses associated 
with the ACURATE Prime XL cohort.   

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Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 11.1.1.3 
Statistical… 
Endpoint – Main 
Randomized Cohort 
For the Main Randomized Cohort… 
Section 11.1.3 
Baseline 
Comparability 
Baseline data will be summarized by treatment group for the 
randomized subjects (Main Randomized Cohort and Extended 
Durability Study) and separately for the Roll-In, ACURATE 
Prime XL Nested Registry, and CAS subjects… No formal 
statistical testing will be done for the Roll-In, Extended Durability 
Study, or ACURATE CAS subjects. 
Section 11.1.4 Post-
procedure 
Measurements 
Post-procedure information… for randomized subjects (Main 
Randomized Cohort and Extended Durability Study), differences 
between… No formal statistical testing will be done for the Roll-
In, Extended Durability Study, or ACURATE CAS subjects. 
Please see Section 11.1.1.1 and Section 11.1.2, respectively, 
regarding statistical testing for the Main Randomized Cohort and 
the ACURATE Prime XL Nested Registry. 
Section 11.2.1 
Analysis Sets 
Subjects in the randomized cohorts (Main Randomized Cohort and 
Extended Durability Study) are considered enrolled… 
With the Roll-In, ACURATE Prime™ XL Nested Registry, and 
ACURATE CAS cohorts, the subject is considered enrolled… 
For the Main Randomized Cohort… 
Section 11.2.4 
Randomization 
Scheme 
For the Main Randomized Cohort and Extended Durability Study, 
a computer-generated list… treatment in a 1:1 ratio of ACURATE 
neo2 to Control. 
Section 11.2.5 
Reporting Events 
For all subjects in the ACURATE IDE Roll-In, ACURATE 
Prime™ XL Nested Registry, and ACURATE CAS cohorts, all 
events that occur from the time of enrollment will be reported. For 
all subjects in the ACURATE IDE randomized cohorts (Main 
Randomized Cohort and Extended Durability Study), events… 

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Table 26.1-1: Revision History 
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Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 11.3.2 
Interim/ 
Administrative 
Analyses 
… when the first 350 subjects in the Main Randomized Cohort 
have completed 1-year… The formal interim analysis will be 
carried out after enrollment in the Main Randomized Cohort is 
completed (see Note 1 below). This formal interim analysis will be 
conducted on the full all (N=1500) Main Randomized Cohort 
subjects after the first 1050 Main Randomized Cohort subjects 
have completed… A final analysis will be performed on all 
subjects in the Main Randomized Cohort with… 
 
Note 1: Analyses of the Extended Durability Study and the 
ACURATE CAS are not expected to occur when the formal 
interim analysis is performed on the Main Randomized Cohort. 
See Section 11.1.2 for information on analyses associated with the 
ACURATE Prime XL cohort. 
Section 11.3.3 
Subgroup Analyses 
for Main 
Randomized Cohort 
Subjects 
Primary and pre-specified additional endpoints will be 
summarized for the following subgroups of the Main Randomized 
Cohort subjects as described… 
Updated for clarity 
Section 11.3.4 
Justification of 
Pooling 
Analyses for the primary endpoint in the Main Randomized 
Cohort will be presented… 
Section 11.3.5 
Multivariable 
Analyses 
… assess the effect of potential predictors on the primary endpoint 
in the Main Randomized Cohort as described… 
Section 16.4.2 
Training with the 
Investigational… 
Note 3: Centers selected to participate in the ACURATE Prime 
XL Nested Registry will receive… 

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Table 26.1-1: Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
Section 18.1 
Anticipated Risks… 
Table 18.1 1: Risks Associated with Transcatheter Aortic Valve 
Replacement – Added Radiation injury 
Section 20. 
Informed Consent 
Note: Centers may use remote consent as allowed by institutional 
policy and the center’s IRB/REB/HREC/IEC. 
Section 26.1 
Summary of 
Protocol Revision 
History 
Updated Table 26.1-1 with revision history associated with 
protocol version M.