Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial

Study Overview
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Brief Summary
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To establish the safety and effectiveness of the Edwards PASCAL Transcatheter Valve Repair System in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT)

Detailed Description
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A prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter mitral valve repair with the Edwards PASCAL Transcatheter Valve Repair System compared to Abbott MitraClip in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT) Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 5 years.

Official Title
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Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial (CLASP IID/IIF): A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Mitral Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System Compared to Abbott MitraClip in Patients With Mitral Regurgitation

Conditions
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Degenerative Mitral Valve Disease, Mitral Regurgitation, Mitral Insufficiency, Functional Mitral Regurgitation

Intervention / Treatment
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* Device: Edwards PASCAL System
* Device: Abbott Mitraclip System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen (18) years of age or older Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow-up visit requirements. Patient is determined to be at prohibitive risk for mitral valve surgery by the heart team (CLASP IID cohort only). Patient is on stable heart failure medications/Guideline Directed Medical Therapy (CLASP IIF cohort only) Patient is determined to be a candidate for transcatheter mitral valve repair by the heart team for both PASCAL and MitraClip Mitral regurgitation (3+ to 4+) by echo Suitable valve and regurgitant jet morphology Elevated corrected BNP > 400 pg/ml or corrected NT-pro BNP of > 900 pg/ml or heart failure hospitalization within the past 12 months (CLASP IIF cohort only) LVEF ≥ 20% (and ≤ 50%; CLASP IIF cohort only) Exclusion Criteria: Patient in whom a TEE is contraindicated or screening TEE is unsuccessful Mitral valve anatomy which may preclude proper PASCAL or MitraClip access, use and/or deployment or sufficient reduction in mitral regurgitation Patient with refractory heart failure requiring advanced intervention (i.e. left ventricular assist device, Status ≤5 heart transplantation) (ACC/AHA Stage D heart failure) Clinically significant, untreated coronary artery disease Recent stroke Other severe valve disorders requiring intervention Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months Any prior mitral valve surgery or transcatheter mitral valve procedure (excluding chordal replacement or surgical annuloplasty repair) Severe tricuspid regurgitation or tricuspid valve disease requiring surgery Active rheumatic heart disease or rheumatic etiology for MR Severe aortic stenosis or regurgitation Known history of untreated, severe carotid stenosis Recent deep vein thrombosis (DVT) or pulmonary embolism (PE) Severe COPD Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to intervention and be adherent to an accepted method of contraception Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator Patient is currently participating in another investigational biologic, drug or device clinical study where the primary study endpoint was not reached at time of enrollment Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edwards PASCAL System - CLASP IID<br>Transcatheter mitral valve repair with the Edwards PASCAL System in patients with degenerative mitral regurgitation | Device: Edwards PASCAL System<br>* Transcatheter mitral valve repair with the Edwards PASCAL System<br>* Other names: Transcatheter Mitral Valve repair (TMVr);|
| Active Comparator: Abbott Mitraclip System - CLASP IID<br>Transcatheter mitral valve repair with the Abbott Mitraclip System in patients with degenerative mitral regurgitation | Device: Abbott Mitraclip System<br>* Transcatheter mitral valve repair with the Abbott Mitraclip System<br>* Other names: Transcatheter Mitral Valve repair (TMVr);|
| Experimental: Edwards PASCAL System - CLASP IIF<br>Transcatheter mitral valve repair with the Edwards PASCAL System in patients on guideline directed medical therapy with functional mitral regurgitation | Device: Edwards PASCAL System<br>* Transcatheter mitral valve repair with the Edwards PASCAL System<br>* Other names: Transcatheter Mitral Valve repair (TMVr);|
| Active Comparator: Abbott Mitraclip System - CLASP IIF<br>Transcatheter mitral valve repair with the Abbott Mitraclip System in patients on guideline directed medical therapy with functional mitral regurgitation | Device: Abbott Mitraclip System<br>* Transcatheter mitral valve repair with the Abbott Mitraclip System<br>* Other names: Transcatheter Mitral Valve repair (TMVr);|
| Experimental: Edwards PASCAL System - Single-Arm Registry<br>Transcatheter mitral valve repair with the Edwards PASCAL System in patients with mitral regurgitation who were deemed non-randomizable by a central screening committee (CSC) due to complex anatomical features described in the current MitraClip Instructions for Use (IFU) but were considered suitable for the PASCAL system. | Device: Edwards PASCAL System<br>* Transcatheter mitral valve repair with the Edwards PASCAL System<br>* Other names: Transcatheter Mitral Valve repair (TMVr);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASCAL is not inferior to MitraClip with respect to the proportion of patients with major adverse events (MAE). The primary safety endpoint is a composite of Major Adverse Events (MAEs). |  | 30 days. | 
| PASCAL is not inferior to Mitraclip with respect to the proportion of patients with MR severity reduction as measured by echocardiography using a scale of 0-4+ for the CLASP IID Cohort. |  | 6 months | 
| PASCAL is not inferior to Mitraclip with respect to the time to first heart failure hospitalization or death for the CLASP IIF Cohort only. |  | From date of randomization until date of first heart failure hospitalization or death, through 5 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of various adverse events | Rates of various adverse events at 6 and 12 months | 6 months; 12 months | 
| Functional Improvement (increase in 6 minute walk test in meters) | Increase in 6 minute walk test in meters | 30 days , 6 months, 1 year | 
| Functional improvement (quality of life) as assessed using the Kansas City Cardiomyopathy Questionnaire through 2 years | Number of points of improvement on a scale of 0-100 in Kansas City Cardiomyopathy Questionnaire, with higher scores associated with higher Quality of Life | 30 days , 6 months, 1 year, 2 year | 
| Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (SF-36) questionnaire through 2 years | Number of points of improvement on a scale of 0-100 in Short Form Health Survey (SF-36) questionnaire, with higher totals associated with higher Quality of Life | 30 days, 6 months, 1 year, 2 year | 
| Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (EQ-5D-5L) questionnaire through | Number of points of improvement on a scale of 1-100 in Short Form Health Survey (EQ-5D-5L) questionnaire, with higher totals associated with higher Quality of Life | 30 days, 6 months, 1 year, 2 year |