SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

Study Overview
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Brief Summary
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The purpose of this trial is to generate clinical evidence on valve safety and performance of self-expanding (SE) versus balloon-expandable (BE) transcatheter aortic valve replacement (TAVR) in subjects with a small aortic annulus and symptomatic severe native aortic stenosis. Additionally, a stress echocardiography sub-study will be conducted as part of the SMART Trial at select sites. The purpose of the sub-study is to evaluate performance of SE versus BE TAVR in subjects with a small aortic annulus and symptomatic severe native aortic stenosis after undergoing exercise stress echocardiographic testing.

Detailed Description
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This is a prospective, multi-center, international, randomized controlled, post-market trial. The primary objectives of the trial are to demonstrate clinical non-inferiority and hemodynamic superiority of the Evolut PRO/PRO+/FX System when compared to subjects treated with the SAPIEN 3/3 Ultra System at 12 months post-procedure. Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE Transcatheter Aortic Valve (TAV) or an Edwards BE Transcatheter Heart Valve (THV). Data will be collected at pre- and post-procedure, at discharge, at 30 days, and once a year until the 5-year follow-up is completed. Product Names: Medtronic Evolut PRO and Evolut PRO+ TAV Systems, Evolut FX System (Commercially available in the United States and may be used upon commercial availability in Canada.) Edwards SAPIEN 3 and SAPIEN 3 Ultra THV Systems The exercise stress echocardiographic testing at select SMART Trial sites seeks to evaluate the performance of the prosthetic aortic valve during exercise. The stress echocardiogram assessment will be conducted as part of the 12-month visit for participating subjects.

Official Title
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SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

Conditions
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Symptomatic Aortic Stenosis, Aortic Valve Stenosis, Aortic Valve Replacement

Intervention / Treatment
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* Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems
* Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart Team agrees that the subject is deemed symptomatic and is a candidate for transcatheter aortic valve replacement (TAVR) Subject has a predicted risk of operative mortality < 15% as determined by the local Heart Team Subject has severe aortic stenosis as determined by transthoracic echocardiography (TTE) at rest Subject has a small aortic annulus as determined by Multi-detector computed tomography (MDCT) Subject's anatomy is appropriate for both Medtronic Evolut PRO/PRO+/FX TAV and Edwards SAPIEN 3/3 Ultra TAV Subject's anatomy is suitable for TAVR via transfemoral vessel access Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits Exclusion Criteria: Estimated life expectancy of fewer than 2 years Multivessel coronary artery disease with a Syntax score >32 and/or unprotected left main coronary artery(Syntax score calculation is not required for patients with history of previous revascularization if repeat revascularization is not planned). Participating in another trial that may influence the outcome of this trial Need for an emergent procedure for any reason Contraindicated for treatment with the Evolut PRO/PRO+/FX and Edwards SAPIEN 3/3 Ultra TAV in accordance with the Instructions for Use Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams Pregnant, nursing, or planning to be pregnant Subject is less than the legal age of consent, legally incompetent, unable to provide his/her own informed consent, or otherwise vulnerable Subject has an active COVID-19 infection or relevant history of COVID-19 Previous aortic valve replacement

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medtronic Self-Expanding TAV<br>Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV. | Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems<br>* TAVR treatment with Medtronic Evolut PRO, PRO+ System or Evolut FX System (where commercially available)<br>|
| Experimental: Edwards Balloon-Expandable THV<br>Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV. | Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems<br>* TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality, disabling stroke or heart failure rehospitalization | Percentage of participants with all-cause mortality, disabling stroke, or heart failure rehospitalization. | 12 months | 
| Bioprosthetic Valve Dysfunction (BVD) | Percentage of participants with BVD (hemodynamic structural valve dysfunction, non-structural valve dysfunction, thrombosis, endocarditis, or aortic valve re-intervention) at 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with BVD in female subjects |  | 12 months | 
| Percentage of participants with Hemodynamic Structural Valve Dysfunction (HSVD) |  | 12 months | 
| Aortic valve mean gradient as a continuous variable |  | 12 months | 
| Effective Orifice Area (EOA) as a continuous variable |  | 12 months | 
| Rate of moderate or severe prothesis-patient mismatch (PPM) |  | 30 days |