HighLife™ Transcatheter Mitral Valve Replacement System Study

Study Overview
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Brief Summary
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Multicenter feasibility study of the HighLife™ TMVR system.

Detailed Description
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This is an exploratory clinical study designed to evaluate the feasibility, safety and performance of the Highlife TMVR System in a population of patients with severe symptomatic mitral regurgitation, who are not suitable for surgical or approved percutaneous treatments according to the judgement of the Heart Team. The data gathered in this study will allow to evaluate the feasibility of mitral replacement using the HighLife™ TMVR system and characterize the safety and performance profile of the HighLife™ TMVR System. All patients will be followed periodically up to 12 months after the intervention and long term safety and performance will be collected annually up to 5 years.

Official Title
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HighLife™ Transcatheter Mitral Valve Replacement System for Severe Mitral Regurgitation in Patients at High Surgical Risk

Conditions
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Mitral Valve Regurgitation, Mitral Valve Insufficiency

Intervention / Treatment
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* Device: Transcatheter Mitral Valve Replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Severe mitral regurgitation New York Heart Association (NYHA) Functional Class II, III or ambulatory IV. Patient is under maximally tolerated GDMT (incl. CRT) for at least 3 months Multidisciplinary Heart Team consensus that the patient is inoperable or at high-risk for surgical repair/replacement due to significant co-morbid conditions Multidisciplinary Heart Team consensus that the patient is not a suitable candidate for other approved percutaneous repair therapy due to anatomical or medical conditions Patient meets the anatomical criteria for HighLife valve sizing as determined by CT and TEE Main Exclusion Criteria: Mitral stenosis Rheumatic valve disease Severe calcifications of the mitral annulus and/or mitral leaflets Prior surgical or interventional treatment of the mitral valve Unsuitable anatomy for the transapical access Unsuitable anatomy of the aorta and ilio-femoral vessels for the transfemoral access Untreated clinically significant coronary artery disease requiring revascularization LVEF < 30% LVEDD > 70mm Echocardiographic evidence of intracardiac mass, thrombus or vegetation Hypertrophic Obstructive Cardiomyopathy (HOCM) Any surgical or interventional procedure (including PCI) done in the past 30 days prior to procedure

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: transcatheter mitral valve replacement<br>HighLife TMVR System is a novel and innovative approach developed as an alternative treatment for severe MR when medical treatment is maximal and surgical interventions not possible or at high risk. The HighLife TMVR system is composed of a Transcatheter Mitral Valve (TMV), a sub-annular implant (SAI), and their delivery systems and loading tools. The HighLife Valve is a 31 mm mitral bioprosthesis made of a self-expanding Nitinol frame covered with polyester graft and supporting bovine pericardium leaflets. The bioprosthesis is used in conjunction with the Sub-Annular Implant (SAI). | Device: Transcatheter Mitral Valve Replacement<br>* Minimally invasive transcatheter mitral valve implantation using the HighLife™ TMVR system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom of major adverse events | including: All-cause mortality Myocardial infarction or coronary ischemia requiring PCI or CABG Major stroke Life-threatening bleeding (MVARC scale) 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 Severe hypotension, heart failure or respiratory failure requiring intravenous pressors 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 ≥ 48H | at 30 days post procedure | 
| Continued intended performance of the HighLife™ bioprosthesis | defined as the reduction of mitral regurgitation (MR) to either optimal (0+ to trace) or acceptable (reduced by at least 1 grade from baseline with no more than 2+ MR) without significant mitral stenosis (post-procedure EOA ≥ 1.5 cm2 with a transmitral gradient < 5mmHg) and with no greater than mild (1+) paravalvular MR (and without associated hemolysis) | at 30 days post procedure | 
| Technical success | defined as alive patient at exit from procedure room, with all of the following: Successful access, delivery and retrieval of the HighLife delivery systems Deployment and correct positioning of the HighLife bioprosthesis Freedom of additional emergency surgery or re-intervention related to the device or access procedure | immediately after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success (per MVARC definitions) | per MVARC definition | At 30 days, 6 months and 12 months post procedure | 
| Procedure Success | per MVARC definition | At 30 days, 6 months and 12 months post procedure | 
| Patient Success | per MVARC definition | At 30 days, 6 months and 12 months post procedure | 
| Hemodynamic Performance vs. Baseline | Echocardiographic evaluation | At 7 days, 30 days, at 6 months and 12 months and at 2, 3, 4 and 5 years | 
| Functional Improvement vs. Baseline | New York Heart Association Class 6-Minute Walk Test | At 30 days, 6 months and 12 months | 
| Quality of Life Improvement vs. Baseline | Kansas City Cardiomyopathy Questionnaire | At 6 months and 12 months |