Feasibility Study of Patients With Severe MR Treated With the Cardiovalve TMVR System

Study Overview
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Brief Summary
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The study will test the safety and performance of the Cardiovalve transfemoral mitral valve replacement system in treating patients with severe mitral regurgitation who are at high risk for open chest surgery. The system is comprised of comprised of: 1) an Implant; 2) a Delivery System (DS); and 3) Accessories that are required for the implantation procedure. the procedure is performed under general anesthesia.

Detailed Description
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The study will test the safety and performance of the Cardiovalve transfemoral mitral valve replacement system in treating patients with severe mitral regurgitation who are at high risk for open chest surgery. The system is comprised of comprised of: 1) an Implant; 2) a Delivery System (DS); and 3) Accessories that are required for the implantation procedure. The implant procedure is performed under general anesthesia, and the participants will be followed-up at discharge, 1- 3-, 6-, 12- and 24-months post-procedure, in order to check the system functionality and effect on their cardiology status.

Official Title
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Feasibility Study of High Surgical Risk Patients With Severe Mitral Regurgitation Treated With the Cardiovalve Transfemoral Mitral Valve System

Conditions
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Mitral Regurgitation

Intervention / Treatment
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* Device: Implantation


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: 2. NYHA functional II, III or ambulatory IV 3. Severe mitral regurgitation (MR grade 3-4+) with pronounced secondary MR etiology 4. Subject is on optimal guideline-directed medical therapy for heart failure for at least 30 days or CRT if indicated. 5. Elevated risk for conventional open mitral valve repair or replacement surgery in the consideration of the site Heart Team (including a cardiac surgeon, a cardiologist and imaging specialist as a minimum) based on STS/Euro Score II (per MVARC Part 1), frailty and co-morbidities. 6. Able to undergo Transesophageal Echocardiography (TEE). 7. Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed. 8. The subject commits to return for the scheduled post-operative follow-up visits at the hospital. Anatomical Inclusion Criteria 9. Suitable for femoral access procedure and trans septal catheterization 10. Native mitral valve geometry and size and LV outflow tract characteristics compatible with the Cardiovalve (as assessed by the independent Screening Committee) Exclusion Criteria: Cardiovascular Exclusion Criteria Prior stroke or TIA within 3 months or Modified Rankin Scale ≥4 disability Acute myocardial infarction within the previous 30 days 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, or 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 Anatomical Exclusion Criteria (assessed by pre-procedural imaging) Left Ventricular Ejection Fraction (LVEF) <30% LV end diastolic diameter > 70mm Significant abnormalities of the mitral valve and 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 General Exclusion Criteria Subject who is currently participating in an investigational study, other than this study Hemodynamic instability defined as systolic pressure < 90mmHg or the need for inotropic support or intra-aortic balloon pump or other hemodynamic support device, or any mechanical heart assistance Subject has contrast agent hypersensitivity that cannot be adequately pre-medicated, has an allergy to Nitinol alloys (nickel and titanium), or has 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 Patients with renal insufficiency (creatinine > 2.5 mg/dL) 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

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: Implantation<br>Eligible patients will undergo implantation with the Cardiovalve system | Device: Implantation<br>* Implantation of the Cardiovalve transfemoral mitral valve replacement system<br>* Other names: Cardiovalve;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from major device- or procedure- related serious adverse events | Evaluate the safety of the Cardiovalve with its associated procedure | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success of delivery and deployment of the device | Technical success of delivery and deployment of the device in the correct position and retrieval of delivery catheter, without significant mitral stenosis | Intraoperative | 
| Freedom from emergency surgery or reintervention | Freedom from emergency surgery or reintervention related to the device or access procedure | 30 days | 
| Freedom from rehospitalizations or reinterventions due to the underlying condition | Freedom from rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, worsening of heart failure) | 30 days, 3 Months, 6 Months, 12 Months, and 24 Months | 
| Reduction in MR grade | Reduction in MR grade to either optimal (0+ to trace) or acceptable (reduced by at least 1 grade from baseline with no more than 2+ MR) Number of patients with reduction in MR grade from baseline | 30 days, 3-, 6-, 12 and 24-months | 
| NYHA class | Improvement from baseline in NYHA functional class; Number of patients with improvement in NYHA class | 30 days, 3-, 6-, 12 and 24-months | 
| 6 minute walk test | Increase in distance from baseline | 30 days, 3-, 6-, 12 and 24-months | 
| Improvement in quality of life from baseline | Improvement from baseline in quality-of-life (Kansas City Cardiomyopathy Questionnaire improvement by ≥ 10) | 30 days, 3-, 6-, 12 and 24-months |