PROGRESS: Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR

Study Overview
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Brief Summary
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This study objective is to establish the safety and effectiveness of the Edwards SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve systems in subjects with moderate, calcific aortic stenosis.

Detailed Description
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This is a prospective, randomized, controlled, multicenter study. Subjects will be randomized to either transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 / SAPIEN 3 Ultra /SAPIEN 3 Ultra RESILIA THV or Clinical Surveillance.

Official Title
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The PROGRESS Trial: A Prospective, Randomized, Controlled Trial to Assess the Management of Moderate Aortic Stenosis by Clinical Surveillance or Transcatheter Aortic Valve Replacement

Conditions
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Aortic Stenosis, Calcific, Aortic Valve Stenosis

Intervention / Treatment
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* Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 65 years of age or older at time of randomization Moderate aortic stenosis Subject has symptoms or evidence of cardiac damage/dysfunction The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent. Key Exclusion Criteria: Native aortic annulus size unsuitable for the THV Anatomical characteristics that would preclude safe transfemoral placement of the introducer sheath or safe passage of the delivery system Aortic valve is unicuspid or non-calcified Bicuspid aortic valve with an aneurysmal ascending aorta > 4.5 cm or severe raphe/leaflet calcification Pre-existing mechanical or bioprosthetic aortic valve Severe aortic regurgitation Prior balloon aortic valvuloplasty to treat severe AS LVEF < 20% Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVR Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation Coronary or aortic valve anatomy that increases the risk of coronary artery obstruction post-TAVR

Ages Eligible for Study
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Minimum Age: 65 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: TAVR<br>Transcatheter Aortic Valve Replacement (TAVR) | Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA<br>* Patients will be implanted with a SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA heart valve<br>|
| No Intervention: CS<br>Clinical Surveillance (CS) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Effectiveness Endpoint | Non-hierarchical composite of death, and heart failure hospitalization or event | 2 years | 
| Primary Safety Endpoint | Non-hierarchical composite of death, stroke, life threatening or fatal bleeding, acute kidney injury stage 4, hospitalization due to device- or procedure-related complication, and valve dysfunction requiring reintervention | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death, stroke, or unplanned cardiovascular hospitalization | The number of patients that had this event | 2 years | 
| Death, unplanned cardiovascular hospitalization, or decrease of > 10 points in Kansas City Cardiomyopathy Questionnaire (KCCQ) | The number of patients that met all these criteria | 2 years | 
| Unplanned cardiovascular hospitalization | The number of patients that had this event | 2 years | 
| Left ventricle (LV) mass index | Echocardiographic measurement of the size of the left ventricle | 2 years | 
| Stroke volume index | Echocardiographic measurement of the volume of blood pumped out of the left ventricle during contraction. | 2 years | 
| Diastolic dysfunction ≥ Grade 2 | Echocardiographic measurement of the stiffness of the left ventricle. | 2 years | 
| N-Terminal Pro B-type Natriuretic Peptide (NT-ProBNP) | NT-ProBNP is a hormone that measures heart failure. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable. | 2 years | 
| KCCQ overall score | Change from baseline in KCCQ. The KCCQ is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | 2 years | 
| Reduction in LVEF ≥ 5% from baseline AND LVEF < 60% | The number of patients that meet these criteria | 2 years | 
| New onset atrial fibrillation | The number of patients that develop this condition | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter aortic valve replacement (TAVR), SAPIEN 3, SAPIEN 3 Ultra, SAPIEN 3 Ultra RESILIA, Moderate aortic stenosis, Aortic stenosis, Transcatheter heart valve