The CLASP Study Edwards PASCAL TrAnScatheter Mitral Valve RePair System Study

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, performance and clinical outcomes of the Edwards PASCAL Transcatheter Mitral Valve Repair (TMVr) System.

Detailed Description
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The purpose of this study is to assess the safety, performance and clinical outcomes of the Edwards PASCAL Transcatheter Mitral Valve Repair (TMVr) System. This is a multi-center, multi-national, prospective, single arm, safety, performance and clinical outcomes study.

Official Title
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The CLASP Study Edwards PASCAL TrAnScatheter Mitral Valve RePair System Study

Conditions
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Mitral Valve Regurgitation

Intervention / Treatment
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* Device: Mitral Valve Repair


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated IRB/ethics committee approved study consent form prior to study related procedures Eighteen (18) years of age or older New York Heart Association (NYHA) Functional Class II-IVa heart failure despite optimal medical therapy Candidacy for surgical mitral valve repair or replacement determined by Heart Team evaluation Clinically significant mitral regurgitation (moderate-to-severe or severe mitral regurgitation) confirmed by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). The primary regurgitant jet is non-commissural. If a secondary jet exists, it must be considered clinically insignificant. Mitral valve area (MVA) ≥ 4.0 cm² as measured by planimetry. If MVA by planimetry is not measurable, pressure half-time measurement is acceptable. Exclusion Criteria: Patient in whom a TEE is contraindicated or screening TEE is unsuccessful Leaflet anatomy which may preclude PASCAL device implantation, proper device positioning on the leaflets, or sufficient reduction in mitral regurgitation. Mitral valve area (MVA) < 4.0 cm² as measured by planimetry (If MVA by planimetry is not measurable, PHT measurement is acceptable) Echocardiographic evidence of intracardiac mass, thrombus, or vegetation Physical evidence of right sided congestive heart failure and echocardiographic evidence of severe right ventricular dysfunction Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator Patient is currently participating or has participated in another investigational drug or device clinical study where the primary study endpoint was not reached at time of enrollment Patient is under guardianship

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edwards PASCAL Transcatheter Mitral Valve Repair System<br> | Device: Mitral Valve Repair<br>* Minimal Invasive Transcatheter Mitral Valve Repair<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Adverse Events (MAE) | Composite of major adverse events (MAE) defined as cardiovascular mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding and re-intervention for study device related complications at 30 days | 30 days | 
| Device Success | Device is deployed as intended and the delivery system is successfully retrieved as intended at the time of the patient's exit from the cardiac catheterization laboratory. | Exit from the cardiac catheterization laboratory | 
| Number of Participants With Procedural Success | Device success with evidence of mitral regurgitation reduction ≤ MR2+ at discharge and without the need for a surgical or percutaneous intervention prior to hospital discharge. Mitral regurgitation was assessed per independent echocardiography core laboratory. | through discharge | 
| Clinical Success | Procedural success with evidence of MR reduction ≤ MR2+ and without MAEs at 30 days. Mitral regurgitation reduction was assessed per independent echocardiography core laboratory. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitral Regurgitation Reduction | Mitral regurgitation reduction at 30 days, 6 months, 1 year and annually thereafter over baseline. Mitral regurgitation reduction was assessed per independent echocardiography core laboratory. | baseline, 30 days, 6 months, 1 year, 2 year | 
| All-cause Mortality | All-cause mortality at 30 days, 6 months, 1 year and annually thereafter | 30 days, 6 months, 1 year, 2 year | 
| Recurrent Heart Failure Hospitalization | Recurrent heart failure hospitalization at 30 days, 6 months, 1 year and annually thereafter | 30 days , 6 months, 1 year, 2 year | 
| Re-intervention Rates for Mitral Regurgitation | Re-intervention rates for mitral regurgitation at 30 days, 6 months, 1 year and annually thereafter | 30 days, 6 months, 1 year, 2 year | 
| Composite of Major Adverse Events (MAE) Defined as Cardiovascular Mortality, Stroke, Myocardial Infarction, New Need for Renal Replacement Therapy, Severe Bleeding and Re-intervention for Study Device Related Complications | Composite of major adverse events (MAE) defined as cardiovascular mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding and re-intervention for study device related complications at 6 months, 1 year and annually thereafter | 6 months, 1 year, 2 year | 
| Change in Left Ventricular End Diastolic Volume (LVEDV) | Change in Left Ventricular End Diastolic Volume (LVEDV) at 6 months, and 1 year over baseline | 6 months, 1 year, 2 year | 
| Change in Left Ventricular End Systolic Volume (LVESV) | Change in Left Ventricular End Systolic Volume (LVESV) at 6 months and 1 year over baseline | 6 months, 1 year, 2 year | 
| Change in Pulmonary Artery Systolic Pressure | Change in Pulmonary Artery Systolic Pressure at 6 months, and 1 year over baseline | baseline, 6 months, 1 year | 
| Change in Six Minute Walk Test (6MWT) Distance | Mean distance in meters walked during 6 Minute Walk Test (6MWT) at 6 months, and 1 year compared to baseline | 6 months, 1 year | 
| Change in Quality of Life (QoL) Score, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) | Mean KCCQ Score. 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. Scores range from 0-100, in which higher scores reflect better health status. | baseline, 30 days, 6 months, 1 year | 
| Change in Quality of Life (QoL) Score, as Measured by EQ5D | Change in Quality of Life (QoL) score, as measured by EQ5D at 30 days, 6 months over baseline. The EQ5D self-reported questionnaire includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, with higher scores for higher health-related quality of life. | baseline, 30 days, 6 months, 1 year | 
| Change in NYHA Functional Classification | Change in NYHA Functional Classification at 6 months and 1 year over baseline. NYHA Classification - The stages of heart failure: Class I - No symptoms and no limitation in ordinary physical activity. Class II - Mild symptoms and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. | baseline, 6 months, 1 year, 2 year | 
| Change NT-pro-BNP Level | Change in NT-pro-BNP level at 6 months and 1 year and annually thereafter over baseline | baseline, 6 months, 1 year, 2 year | 
| Change in BNP Level | Change in BNP level at 6 months, 1 year and annually thereafter over baseline | baseline, 6 months, 1 year, 2 year | 
| Change in Tricuspid Regurgitation (TR) at 6 Months, 1 Year and Annually Thereafter Over Baseline | Change in TR over baseline at 6 months, and 1 year. TR grade was assessed by an independent echocardiography core lab using a 6-grade scale: None, trace, mild, mild-moderate, moderate-severe, or severe. Reduction by 1 or more grades reflects improvement from baseline, while an increase by 1 or more grades reflects worsening of TR. | 6 months, 1 year, 2 year | 
| Change in Effective Regurgitant Orifice Area (EROA) | Change in effective regurgitant orifice area (EROA) at 30 days, 6 months, 1 year and annually thereafter over baseline. | baseline, 30 days, 6 months, 1 year, 2 year | 
| Change in Mitral Regurgitant Volume | Change in mitral regurgitant volume at 30 days, 6 months, 1 year and annually thereafter over baseline | baseline, 30 days, 6 months, 1 year, 2 year |