Munich Transcatheter Mitral Valve Safety and Effectiveness

Study Overview
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Brief Summary
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The Munich Trascatheter Mitral Valve System is intended for beating heart, mitral valve replacement in patients with a diseased, damaged, or malfunctioning mitral valve. Access is provided through the Femoral Vein and transseptal approach by means of a 27Fr catheter. The bioprosthetic valve consists of a self-expanding, tri-leaflet, dry bovine-pericardial valve. The dry tissue allows the valve to be conveniently pre-loaded. The valve is available in three sizes and has been designed to reduce the complexity of implantation in comparison to other TMVR systems.

Detailed Description
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This is a prospective multicenter clinical investigation designed to evaluate the safety and effectiveness of the Munich TMVR System in a population of patients with moderate to severe, symptomatic mitral regurgitation, who are not suitable for surgical treatments. Patients who meet all of the study inclusion criteria, will be treated with the Munich valve. After the intervention, patients will be followed up closely for 12 months. Long term safety and efficacy data will be collected annually up to 5 years.

Official Title
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Clinical Evaluation of Safety and Effectiveness of the Munich Transcatheter Mitral Valve Replacement (TMVR) System

Conditions
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Mitral Regurgitation, Mitral Valve Disease

Intervention / Treatment
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* Device: MUNICH TRANSCATHETER MITRAL VALVE REPLACEMENT SYSTEM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Moderate or severe mitral regurgitation (> 3+) For Degenerative MR: EROA ≥ 40 mm2 or regurgitant volume ≥ 60ml For Secondary MR: EROA > 30 mm2 or regurgitant volume > 45ml (i.e., MR moderate or severe by ASE criteria) New York Heart Association (NYHA) Functional Class II, III or ambulatory IV Subject is under guideline directed medical therapy for at least one month Subject is high-risk for open-heart surgery based on the assessment of the multidisciplinary Heart Team using standard scoring systems and consideration of co-morbidities, frailty and disability Subject meets the anatomical criteria for Munich TMVR System Patient is willing to participate in the study and provides signed informed consent. Exclusion Criteria: General Conditions Subject who is currently participating in an investigational study, other than this study Subjects allergic to bovine tissue Subjects with uncontrolled hypotension Hemodynamic instability Subject has contrast agent hypersensitivity that cannot be adequately pre-medicated and has an allergy to Nitinol alloys Intolerance to antiplatelet, anticoagulant or thrombolytic medications Bleeding diathesis or hypercoagulable state Active peptic ulcer or active gastrointestinal bleeding Pulmonary artery systolic pressure >70 mmHg Renal insufficiency Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months. Subject with hepatic insufficiency Subject has a co-morbid illness that may result in a life expectancy of less than one year Active infection that requires antibiotic therapy Subject is pregnant, breastfeeding or intend to become pregnant within one year, and female subjects in childbearing age NOT using a highly effective method of contraception with a failure rate of less than 1% per year. Comorbidities Prior stroke or TIA within 3 months or Modified Rankin Scale ≥4 disability Acute myocardial infarction within the previous 30 day Any prior heart valve surgery or transcatheter mitral intervention Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days Rheumatic heart disease or endocarditis within the previous 3 months Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis Severe organic lesion with retracted chordae or congenital malformation and lack of valvular tissue Any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non-ischemic etiology. Existence of inferior vena cava filter or atrial septal device (contraindicating femoral access and transseptal catheterization) Untreated clinically significant coronary artery disease requiring revascularization Tricuspid valve disease requiring surgery or severe tricuspid regurgitation Aortic or pulmonic valve disease requiring surgery CRT/ICD implant within 30 days NYHA class IVb UNOS stadium 1 heart transplantation or previous orthotopic heart transplantation Anatomical and Functional Left Ventricular Ejection Fraction (LVEF) <30% LV end diastolic diameter > 70mm Significant abnormalities of the sub-valvular apparatus. Severe mitral annular or leaflets calcification Left atrial or LV thrombus or vegetation Severe right ventricular dysfunction Severe tricuspid or aortic valve disease

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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Accepts Healthy Volunteers

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
Interventional Model Description: This is a prospective, non-randomized, single-arm, international, multicenter, clinical study designed to evaluate the safety and performance of the P&F MUNICH TMVR System in a population of patients with moderate to severe symptomatic mitral regurgitation, who are not suitable for surgical or approved percutaneous treatments. All patients will be followed closely up to 12 months after the intervention and long-term safety and effectiveness will be collected annually up to 5 years.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Arm<br>This is a prospective, non-randomized, single-arm, international, multicenter, clinical study designed to evaluate the safety, efficacy, and performance of the P&F MUNICH TMVR System in a population of patients with moderate to severe symptomatic Mitral Regurgitation. | Device: MUNICH TRANSCATHETER MITRAL VALVE REPLACEMENT SYSTEM<br>* The replacement valve consists of a self-expanding, tri-leaflet, dry bovine -pericardial valve. The dry tissue allows the valve to be conveniently pre-loaded. The key characteristics of Munich valve are: Nitinol stent frame Bovine pericardium Polyester skirt Anchoring system allows anchoring the frame to the annulus Hooks are used to reduce the mobility of the native leaflets and decrease risk of embolization. The Munich TMVR system design proposed for this clinical investigation represents a significant evolution from previous TMVR designs: Transfemoral / transseptal access Self-expanding Dry pericardium (can be pre-loaded) No anchors 27 Fr delivery catheter ( Sizes: 40/48/55mm Height 30 mm The valve is available in 3 sizes with a 30mm profile and has been designed to reduce the complexity of implantation in comparison to other TMVR systems.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoints | The primary safety endpoint is to evaluate a 30-day major adverse events (MAE) rate, where MAE is a composite of the following device- or procedure-related events: All-cause mortality Stroke Life-threatening bleeding (MVARC scale) Major vascular complications Major cardiac structural complications Myocardial infarction or coronary ischemia requiring PCI or CABG Stage 2 or 3 acute kidney injury (includes new dialysis) Severe hypotension, worsening of heart failure, or respiratory failure requiring intravenous pressor or invasive or mechanical heart failure treatments such as ultraﬁltration or hemodynamic assist devices, including intra-aortic balloon pumps or left ventricular or biventricular assist devices, or prolonged intubation for >48 h. Emergency surgery or re-intervention. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Safety Endpoints | Secondary safety endpoints include an evaluation at 90-day, 180-day, 1 year and annually at year 2, 3, 4 and 5 (inclusive of unscheduled visits): Death, cardiac, non-cardiac Stroke Myocardial Infarction Any device related complication/ dysfunction New atrial fibrillation (AF) New conduction disturbance requiring permanent pacemaker (PM) Major access and vascular complications Stage 2 or 3 acute kidney injury (includes dialysis) Any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention | 90-day, 180-day, 1 year and annually at year 2, 3, 4 and 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitral regurgitation, heart failure