CORCYM Mitral, Aortic aNd Tricuspid Post-maRket Study in a reAl-world Setting

Study Overview
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Brief Summary
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MANTRA is a prospective, multiple-arm, multi-center, global, post-market clinical follow-up study. The main objective is to monitor ongoing safety and performance of the CORCYM devices and accessories used for aortic, mitral and tricuspid valvular diseases in a real-world setting. Corcym S.r.l., is a medical device manufacturer with a broad product portfolio for cardiac surgeons, offering solutions for the treatment of aortic, mitral and tricuspid valve disease. The MANTRA Master Plan (Master Protocol) is intended as an overarching Umbrella Protocol that allows multiple sub-studies to be added, as needed. The Umbrella Master Protocol concept offers an excellent solution to provide post-marketing clinical follow-up information on the entire cardiac surgery heart valve portfolio of the sponsor in a common database, including corelab assessment of hemodynamic and structural performance, annular motion and Dynamics for one of the products. Currently, three sub-studies are planned: MANTRA - Aortic Sub-Study MANTRA - Mitral/Tricuspid Sub-Study (Excluding Memo 4D) MANTRA - Memo 4D Sub-Study

Detailed Description
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The MANTRA Master Plan (Master Protocol) is intended as an overarching Umbrella Protocol that allows multiple substudies to be added, as needed. The Umbrella Master Protocol concept offers an excellent solution to provide post-marketing clinical follow-up information on the entire cardiac surgery heart valve portfolio of the sponsor in a common database. Currently, three substudies are planned: MANTRA - Aortic Sub-Study MANTRA - Mitral/Tricuspid Sub-Study (excluding Memo 4D) MANTRA - Memo 4D Sub-Study The aim of the studies assembled under the master protocol is the continued collection of safety and performance data during heart valve procedures and the relevant follow-up visits in subjects where any of the CORCYM devices and accessories are used in a real-world setting, in accordance with the IFUs, and at the discretion of the investigator. MANTRA study is expected to enroll approximately 2150 subjects in up to 130 sites worldwide: Approximately 1650 subjects considered suitable for treatment with a CORCYM aortic device Approximately 300 subjects considered suitable for treatment with a CORCYM mitral and/or tricuspid device (excluding Memo 4D) Approximately 200 subjects considered suitable for treatment with Memo 4D Expected enrollment duration may vary across the different projects. Subject follow-up is planned at discharge, 30 days after implantation and then annually up to 10 years. Sites can choose to participate in one or more sub-studies. All available data shall be gathered during standard medical care. At a minimum, the following data will be collected: Informed Consent Screening/Baseline data, including demographics and medical history Procedural data Hospitalization and Discharge data Follow-up data: 30 days and annually up to 10 years post procedure Serious Adverse Event and Device Deficiencies information As part of the study, the subject will be asked to complete quality of life questionnaire(s) at baseline, 30 days and at 1-year follow-up. In addition, for the MEMO 4D sub-study only, an Echocardiography Core Laboratory has been appointed by the Sponsor to assess the hemodynamic and structural performance, annular motion and dynamics, and 3D echocardiogram images (transesophageal during the procedure and transthoracic during follow up) will be collected for Corelab readings.

Official Title
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CORCYM Mitral, Aortic aNd Tricuspid Post-maRket Study in a reAl-world Setting

Conditions
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Cardiac Valve Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated approved Informed Consent Subject is willing and able to comply with the follow up schedule of the protocol Eligible for treatment with CORCYM aortic, mitral and/or tricuspid products as outlined in the applicable Instructions for Use (IFU) Exclusion Criteria: Subject is already participating to another clinical investigation that could confound the results of this clinical investigation. Subject has a life expectancy ≤ 12 months Subject has contraindications to the use of CORCYM aortic, mitral and/or tricuspid devices as outlined in the applicable Instructions For Use (IFU)
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MANTRA Aortic Sub-study<br>Subjects diagnosed with aortic valve disease who are considered suitable to undergo aortic valve replacement with a CORCYM device can be included in this study. The following devices can be entered in the study: Tissue Valve: Perceval® PLUS SUTURELESS AORTIC HEART VALVE Perceval® S SUTURELESS AORTIC HEART VALVE Mechanical Valves: Bicarbon™ Bileaflet Heart Valve Prostheses Models: Bicarbon Fitline Aortic (LFA) Bicarbon Slimline Aortic (LSA) Bicarbon Overline Aortic (LOV) Carbomedics Prosthetic Heart Valve Models: Standard Aortic Valve Reduced Aortic Valve Supra-Annular Aortic Valve (Top Hat) Orbis™ Aortic Valve Ascending Aorta Prostheses CARBOMEDICS-CARBO-SEAL™ CARBOMEDICS CARBO-SEAL™ VALSALVA | |
| MANTRA Mitral/Tricuspid Sub-study<br>Subjects diagnosed with mitral and/or tricuspid valve disease who are considered suitable to undergo mitral valve repair/replacement and/or tricuspid valve repair with a CORCYM device can be included in this study. The following devices can be entered in the study: Annuloplasty Rings: SOVERING™ ANNULOPLASTY DEVICE models annuloplasty ring, mitral model annuloplasty band, mitral and tricuspid models Carbomedics Annuloplasty Ring models: CARBOMEDICS ANNULOFLO® CARBOMEDICS ANNULOFLEX® Memo Annuloplasty Ring o MEMO 3D™ SEMIRIGID ANNULOPLASTY RING Mitral Valves: Bicarbon™ Bileaflet Heart Valve Prostheses Models: o Bicarbon Fitline Mitral (LFM) Carbomedics Prosthetic Heart Valve Models: Standard Mitral Valve Orbis™ Mitral Valve OptiForm® Mitral Valve | |
| MANTRA Memo 4D Sub-study<br>Subjects diagnosed with mitral valve disease who are considered suitable to undergo mitral valve repair with a CORCYM Memo 4D annuloplasty ring can be included in this study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint in the AORTIC Sub-study is number and percentage of subjects with Device Success | Device success at 30 days (+14 days) based on VARC-3, defined as: Technical success Freedom from mortality Freedom from surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication Intended performance of the valve (mean gradient<20 mmHg and less than moderate aortic regurgitation) The number and percentage of subjects with device success at 30 days as per VARC-3 definition, along with individual component of the success, will be presented. | 30 days | 
| The primary endpoint in the MITRAL/TRICUSPID Sub-study is number and percentage of subjects with Device Success | Device success at 30 days (+14 days) based on MVARC, defined as: Procedural mortality or stroke AND Proper placement and positioning of the device AND Freedom from unplanned surgical or interventional procedures related to the device or access procedure AND Continued intended safety and performance of the device, including: Evidence of structural or functional failure Specific device-related technical failure issues and complications MITRAL: Reduction of Mitral Regurgitation (MR) to either optimal or acceptable levels (site-reported) TRICUSPID: Reduction of Tricuspid Regurgitation (TR) to either optimal or acceptable levels (site-reported) Number and percentage of subjects with device success, along with individual component, will be presented. | 30 days | 
| The primary endpoint in the MEMO 4D Sub-study is number and percentage of subjects with Device Success | Device success at 30 days (+14 days) based on the MVARC, defined as: Procedural mortality or stroke; AND Proper placement and positioning of the device; AND Freedom from unplanned surgical or interventional procedures related to the device or access procedure; AND Continued intended safety and performance of the device, including: Evidence of structural or functional failure Specific device-related technical failure issues and complications Reduction of Mitral Regurgitation (MR) to either optimal or acceptable levels without significant mitral stenosis (i.e., post-procedure EOA is ≥ 1.5 cm2 with a transmitral gradient <5 mmHg), and with no greater than mild MR core-lab assessed The number and percentage of subjects with device success at 30 days as per MVARC definition, along with individual component of the success, will be presented. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality (all-cause mortality, cardiovascular mortality, device related mortality) | Number of patients with this event | up to 10 years from implant | 
| Major Adverse Cardiovascular and Cerebrovascular Event (MACCE - composite endpoint of all cause death, myocardial infarction, stroke, and valve re-intervention) | Number of patients with this event | up to 10 years from implant | 
| Re-hospitalization (all-cause re-hospitalization, cardiovascular re-hospitalization, device related re-hospitalization) | Number of patients with this event | up to 10 years from implant | 
| Technical success | Technical success, defined as successful delivery, correct positioning and deployment of the first intended device intraoperatively | intraoperatively | 
| Clinical Efficacy (AORTIC sub-study) | Clinical Efficacy according to VARC-3 guidelines | 12 months | 
| Valve-related long-term clinical efficacy | Valve-related long-term clinical according to VARC-3 guidelines | at 5 years and up to 10 years | 
| Bioprosthetic Valve Dysfunction (BVD), including Structural Valve Deterioration (SVD), Non structural valve dysfunction (NSVD), Thrombosis and Endocarditis | Number of patients with this event | up to 10 years from implant | 
| Patient outcome (Kansas City Cardiomyopathy Questionnaire (KCCQ-12); and EQ-5D-5L (in patients treated with Perceval Plus) | Quality of life improvement from baseline up to 12 months | 12 months | 
| Patient outcome (New York Heart Association (NYHA) Classification) | Change of New York Heart Association (NYHA) functional class from baseline up to 12 months after implant, and at each subsequent follow-up | up to 10 years from implant | 
| Hemodynamic and structural performance | Main hemodynamic parameters will be collected according to the different indications (Aortic, Mitral and Tricuspid) | up to 10 years from implant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Replacement, Mitral Valve Replacement, Mitral Valve Repair, Tricuspid Valve Repair