ACURATE IDE: Safety and Effectiveness Study of ACURATE Valve for Transcatheter Aortic Valve Replacement

Aortic Stenosis Clinical Trial

Official title:

ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve Through Implantation of ACURATE in Subjects InDicatEd for TAVR

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03735667
• Other study ID #: S2408
• Status: Recruiting
• Phase: N/A
• Start date: June 10, 2019
• Est. completion date: November 2034

Study information

• Verified date: June 2024
• Source: Boston Scientific Corporation
• Contact: Lisa Currier
• Phone: 508-683-4927
• Email: Lisa.Currier[@]bsci.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Subjects will be enrolled at up to 85 centers in the United States, Canada, Europe, and Australia. There will be up to 2,820 subjects in ACURATE IDE.

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 up to 1,500 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™ Aortic Bioprosthesis (transfemoral delivery; Boston Scientific Corporation, Marlborough, MA, USA) will perform at least 2 roll-in cases 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.

• 4D CT Imaging Substudy: Selected centers with the ability to perform high quality 4D computer 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.

• 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 Extended Durability Study: An additional 1:1 randomized study (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]) 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. Data from subjects in the Extended Durability Study will be summarized separately from other cohorts.

• ACURATE Continued Access Study (CAS): An additional cohort of subjects receiving ACURATE neo2 (S, M, and L valve sizes) or ACURATE Prime XL. Data from subjects in the ACURATE CAS will be summarized separately from other cohorts and will be used to further assess performance and safety.

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. Enrolled subjects who do not have a study device implanted will be assessed through 1-year post-procedure for safety/adverse events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2820
• Est. completion date: November 2034
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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: 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); 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 the 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.

• 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.

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 D76).

• 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.

• 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.

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: 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.

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis

Intervention

Device:
• ACURATE neo2™ Transfemoral TAVR System
ACURATE neo2™ Transfemoral TAVR system: Support frame made of nitinol, supra-annular processed tri-leaflet porcine pericardial valve and an outer skirt to limit paravalvular regurgitation (manufactured by Boston Scientific Corporation, Marlborough, MA, USA).
• Medtronic CoreValve TAVR System
Medtronic CoreValve Evolut R or Evolut PRO Transcatheter Aortic Valve Replacement (TAVR) System (or any future Corevalve iterations): The support frame is manufactured from nitinol, which has multilevel, self-expanding properties and is radiopaque. The bioprosthesis is manufactured by suturing valve leaflets and a skirt from porcine pericardium into a tri-leaflet configuration (manufactured by Medtronic CoreValve LLC, Santa Ana, USA).
• Edwards SAPIEN 3 TAVR System
Edwards SAPIEN 3 TAVR system (or any future SAPIEN iterations): balloon-expandable transcatheter aortic bioprosthesis, support frame made of cobalt-chromium, three leaflets constructed of processed bovine pericardial tissue and an outer polyethylene terephthalate (PET) sealing cuff to mitigate paravalvular regurgitation (manufactured by Edwards Lifesciences, Inc., Irvine, California, USA)
• ACURATE Prime™ Transfemoral TAVR System XL
ACURATE Prime™ Transfemoral TAVR system: Support frame made of nitinol, supra-annular processed tri-leaflet porcine pericardial valve and an outer skirt to limit paravalvular regurgitation (manufactured by Boston Scientific Corporation, Marlborough, MA, USA).

Locations

Country	Name	City	State
Canada	London Health Sciences	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	Institut de Cardiologie de Montreal	Montréal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)	Québec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Providence Health - St. Paul's Hospital	Vancouver	British Columbia
United States	Albany Medical Center	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital (Midtown)	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Austin Heart	Austin	Texas
United States	Union Memorial Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore-Jack D. Weiler Hospital	Bronx	New York
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Kaleida Health	Buffalo	New York
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Lindner Center for Research and Education at Christ Hospital	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Mount Carmel Columbus Cardiology Consultants	Columbus	Ohio
United States	OhioHealth Research and Innovation Institute	Columbus	Ohio
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Presbyterian Hospital of Dallas	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Englewood Health	Englewood	New Jersey
United States	NorthShore University Health Study Coordinator	Evanston	Illinois
United States	Providence Regional Medical Center	Everett	Washington
United States	Bellin Health	Green Bay	Wisconsin
United States	UPMC - Pinnacle	Harrisburg	Pennsylvania
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	St. Vincent's Hospital	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Scripps Clinic	La Jolla	California
United States	Baptist Health Medical Center	Little Rock	Arkansas
United States	South Denver Cardiology Associates PC	Littleton	Colorado
United States	Cedars-Sinai Heart Institute	Los Angeles	California
United States	Kaiser Permanente Los Angeles	Los Angeles	California
United States	Aurora Research Institute	Milwaukee	Wisconsin
United States	Medical College of Wisconsin - Froedtert Hospital	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	St Thomas Ascension	Nashville	Tennessee
United States	Robert Wood Johnson Medical Center	New Brunswick	New Jersey
United States	Columbia University Medical Center/NYPH	New York	New York
United States	Cornell Presbyterian - New York	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Orlando Regional Medical Center	Orlando	Florida
United States	Banner Good Samaritan	Phoenix	Arizona
United States	UPMC Pittsburgh	Pittsburgh	Pennsylvania
United States	Baylor Regional Medical Center at Plano	Plano	Texas
United States	Providence Heart Institute	Portland	Oregon
United States	University of California, Davis Medical Center	Sacramento	California
United States	CentraCare Heart and Vascular Center	Saint Cloud	Minnesota
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	St. Joseph's Hospital-St. Paul	Saint Paul	Minnesota
United States	Methodist Healthcare System of San Antonio dba Methodist Hospital	San Antonio	Texas
United States	Kaiser Permanente - San Francisco	San Francisco	California
United States	HonorHealth Scottsdale Healthcare	Scottsdale	Arizona
United States	Sacred Heart Medical Center - Riverbend	Springfield	Oregon
United States	St. John's Hospital (Prairie)	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	TMC HealthCare	Tucson	Arizona
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	University of Massachusetts	Worcester	Massachusetts
United States	Lankenau	Wynnewood	Pennsylvania
United States	WellSpan York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality: all-cause, cardiovascular, and non-cardiovascular	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Stroke: disabling and non-disabling	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Myocardial infarction (MI): periprocedural (=72 hours post index procedure) and spontaneous (>72 hours post index procedure)	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Bleeding: life-threatening (or disabling) and major	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4 and 5 years.
Other	Major vascular complications	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4 and 5 years.
Other	Number of participants with a repeat procedure for valve-related dysfunction (surgical or interventional therapy)	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of Participants with hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV)	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with new permanent pacemaker implantation resulting from new or worsened conduction disturbances	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with new onset of atrial fibrillation or atrial flutter	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Acute kidney injury (AKI; =7 days post index procedure): based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 7 days post index procedure.
Other	Number of participants with Coronary obstruction: periprocedural	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed through 72 hours post index procedure
Other	Number of participants with Ventricular septal perforation	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed through 72 hours post index procedure
Other	Number of participants with Mitral apparatus damage: periprocedural	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed through 72 hours post index procedure
Other	Number of participants with Cardiac tamponade: periprocedural	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed through 72 hours post index procedure
Other	Number of participants with Valve migration	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Valve embolization	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Ectopic valve deployment	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Transcatheter aortic valve (TAV)-in-TAV deployment	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Prosthetic aortic valve thrombosis	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Prosthetic aortic valve endocarditis	Safety endpoint adjudicated by an independent Clinical Events Committee (CEC)	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years.
Other	Number of participants with Successful vascular access, delivery and deployment of the study valve, and successful retrieval of the delivery system (site reported assessment)	Device Performance endpoint, as measured by site reported data	Participants will be followed for the duration of their procedure, an expected average of 1 day (peri- and post-procedure)
Other	Grade of aortic valve regurgitation: paravalvular, central and combined (echocardiographic assessment)	Device Performance endpoint, as assessed by Echocardiographic Core Laboratory	Participants will be followed for the duration of their procedure, an expected average of 1 day (peri- and post-procedure)
Other	Number of participants with Device Success	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/cm2 and iEOA >0.70 cm2/m2 for BMI =30 kg/cm2 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)	Participants will be followed for the duration of their procedure, an expected average of 1 day (post-procedure)
Other	Prosthetic aortic valve performance; Effective Orifice Area (EOA	Effective Orifice Area (EOA), as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	Prosthetic aortic valve performance; Mean Aortic Gradient	Mean aortic gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	Prosthetic aortic valve performance; Peak Aortic Gradient	Peak Aortic Gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	Prosthetic aortic valve performance; Peak Aortic Velocity	Peak Aortic Velocity as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	Prosthetic aortic valve performance; Grade of Aortic Regurgitation	Grade of Aortic Regurgitation as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	New York Heart Association (NYHA) Functional Status classification	Evaluated by New York Heart Association (NYHA) classification	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4, 5, 7 and 10 years.
Other	Neurological status; National Institutes of Health Stroke Scale (NIHSS) Assessment	- National Institutes of Health Stroke Scale (NIHSS) at discharge and 1 year	Participants will be followed at discharge and 1 year.
Other	Neurological status; Modified Rankin Scale (mRS) Assessment	- Modified Rankin Scale (mRS) at discharge and all follow-up visits through 5 years	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1, 2, 3, 4 and 5 years.
Other	Neurological status; Neurological physical exam assessment	- Neurological physical exam in all subjects where stroke is suspected	Participants will be followed for the duration of the trial, through 10 years.
Other	Health Status; Kansas City Cardiomyopathy Quality of Life questionnaire Assessment	Evaluated by Kansas City Cardiomyopathy Quality of Life questionnaire	Participants will be followed for the duration of hospital stay, through 30 days, 1 and 5 years.
Other	Health Status; SF-12 Quality of Life questionnaire Assessment	Evaluated by SF-12 Quality of Life questionnaire	Participants will be followed for the duration of hospital stay, through 30 days, 1 and 5 years.
Primary	Composite rate of all-cause mortality, all stroke, and rehospitalization at 1 year in the Main Randomized Cohort.	Primary Effectiveness Endpoint; A Clinical Events Committee (CEC), independent group of physician experts was used to evaluate all reported cases of death and stroke to determine whether they met the specific protocol definition of the event. It is the CEC adjudicated result that is used in the endpoint analysis.	Participants will be followed for the duration of hospital stay, through 1 year