ALLIANCE: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve

Study Overview
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Brief Summary
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The objective of this study is to establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects with symptomatic, severe, calcific aortic stenosis (AS).

Detailed Description
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This is a prospective, single arm, multicenter study. Subjects with bicuspid aortic valve morphology will be enrolled in a separate registry.

Official Title
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Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve

Conditions
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Aortic Stenosis, Severe

Intervention / Treatment
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* Device: SAPIEN X4 THV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe, calcific AS Native aortic annulus size suitable for SAPIEN X4 THV NYHA functional class ≥ II The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent. Exclusion Criteria: Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system Aortic valve is unicuspid, bicuspid or non-calcified Pre-existing mechanical or bioprosthetic valve in any position Severe aortic regurgitation (> 3+) Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months Left ventricular ejection fraction < 20% Cardiac imaging evidence of intracardiac mass, thrombus or vegetation Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant PVL after THV implantation Increased risk of coronary artery obstruction after THV implantation Myocardial infarction within 30 days prior to the study procedure Hypertrophic cardiomyopathy with subvalvular obstruction Subjects with planned concomitant ablation for atrial fibrillation Complex coronary artery disease (CAD) that cannot be optimally treated by percutaneous coronary intervention (PCI) Any surgical or transcatheter procedure within 30 days prior to the study procedure (unless part of planned strategy for treatment of CAD). Implantation of a permanent pacemaker or implantable cardioverter defibrillator (ICD) is not considered an exclusion. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure (unless part of planned strategy for treatment of CAD) Endocarditis within 180 days prior to the study procedure Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure Renal insufficiency and/or renal replacement therapy Leukopenia, anemia, thrombocytopenia Inability to tolerate or condition precluding treatment with antithrombotic therapy Hypercoagulable state or other condition that increases risk of thrombosis Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication Subject refuses blood products BMI > 50 kg/m2 Estimated life expectancy < 24 months Female who is pregnant or lactating Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments Participating in another investigational drug or device study that has not reached its primary endpoint Subject considered to be part of a vulnerable population
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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVR - Main Cohort<br>Subjects will undergo transcatheter aortic valve replacement (TAVR) | Device: SAPIEN X4 THV<br>* Implantation of the SAPIEN X4 valve<br>|
| Experimental: TAVR - Bicuspid Registry<br>Subjects with bicuspid aortic valve morphology will undergo TAVR | Device: SAPIEN X4 THV<br>* Implantation of the SAPIEN X4 valve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-hierarchical composite of death and stroke | The number of patients that died or had a stroke | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Favorable outcome per VARC-3: Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥ 60, and 3) KCCQ score decrease ≤10 points from baseline | The number of patients that met all of these criteria. The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | 1 year | 
| Paravalvular leak | Paravalvular leak will be categorized as None, Trace, Mild, Mild-Moderate, Moderate, Moderate-Severe, or Severe | 30 days | 
| New permanent pacemaker implantation | The number of patients with this event | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter aortic valve replacement (TAVR), Transcatheter aortic valve implantation (TAVI), SAPIEN X4