First-In-Human Clinical Study for Treatment of Severe Mitral Valve INsufficiency With Epygon™ TRanscatheter Mitral VAlve System

First-In-Human Clinical Study for Treatment of Severe Mitral Valve INsufficiency With Epygon™ TRanscatheter Mitral VAlve System (MINERVA FIH)

The EPYGON VALVE is an innovative mitral valve, intended for valve replacement of a native mitral valve through a minimally invasive implant procedure by means of a dedicated implant device.

The EPYGON VALVE is a bio prosthesis, composed by a functional assembly of bovine pericardium on a NiTinol stent.

The purpose of this trial is to assess the safety and feasibility of the Epygon™ Transcatheter mitral valve and the transapical delivery system, in adult patients with severe, symptomatic mitral regurgitation.

Study Overview

• Status: Recruiting
• Conditions: Mitral Valve Regurgitation
• Intervention / Treatment: Device: Epygon™ Transcatheter Mitral Valve System

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christophe Giot; Phone Number: +33 4 42 95 12 20; Email: christophe.giot@affluentmedical.com

Study Locations

• Austria
  • Innsbruck, Austria
    • Recruiting
    • Medical University of Innsbruck
    • Contact: Nikolaos Bonaros
  • Vienna, Austria
    • Recruiting
    • Medical University of Vienna - Department of Surgery, Division of Cardiac Surgery
    • Contact: Martin Andreas
• Italy
  • Firenze, Italy
    • Recruiting
    • Careggi Hospital Florence Italy Largo Brambilla
    • Contact: Pierluigi Stefano
  • Torino, Italy
    • Recruiting
    • A.O.U. Città della Salute e Della Scienza di Torino
    • Contact: Mauro Rinaldi
• Serbia
  • Belgrade, Serbia
    • Not yet recruiting
    • Dedinje Cardiovascular Institute
    • Contact: Slobodan Micovic
• Spain
  • Badalona, Spain
    • Recruiting
    • Hospital German Trias i Pujol
    • Contact: Christian Munoz Guijosa
  • Barcelona, Spain
    • Recruiting
    • Hospital De La Santa Creu I Sant Pau
    • Contact: Antonino Ginel Iglesias
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Luis Carlos Maroto Castellanos
  • Murcia, Spain
    • Recruiting
    • Hospital Virgen de la Arrixaca
    • Contact: Sergio Canovas Lopez
  • Sevilla, Spain
    • Not yet recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: José Miguel Borrego Dominguez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients of age ≥ 60 years.
2. Patients with primary or secondary severe symptomatic mitral valve regurgitation.
3. Patients with severe, symptomatic mitral regurgitation and who have been evaluated by a multidisciplinary Heart Team and deemed to be ineligible for conventional valve surgery and not eligible for transcatheter repair.
4. Patients with a left ventricular ejection fraction ≥ 30%.
5. Patients in NYHA functional classes III to IV.
6. Patients who have clearly accepted participation in this clinical study and who have signed the informed consent.
7. Patients who are willing to accept and undergo all protocol related requirements.
8. Patients not planning to transfer abroad.

Exclusion Criteria:

- Clinical exclusion criteria (preoperative screening)

1. Patients involved in other clinical assessments for drugs or devices that could interfere or alter the study endpoints.
2. Patients with clinical/anatomical conditions unsuitable for a transapical surgical approach.
3. Patients who have previously undergone implantation of a transcatheter aortic valve prosthesis.
4. Patients with previous implantation of a mitral heart valve prosthesis.
5. Patients with previous implantation of a mitral annuloplasty ring.
6. Patients needing emergency or life-saving interventions.
7. Patients with a heavily calcified mitral annulus and/or anterior mitral leaflet.
8. Patients with active infection or endocarditis (suspect endocarditis included).
9. Patients with echocardiographic evidence of intracardiac mass or thrombus.
10. Patients which suffered an acute myocardial infarction within 30 days of the intended treatment (defined as: Q wave MI, or non-Q wave MI with elevation of CK-MB ≥ 3 times normal in the absence of pathological Q waves), if no assay for CK-MB was performed, elevation of CK level to >2 times normal without new Q waves, or elevated Troponin level is also considered a non-Q wave MI).
11. Patients with an active peptic ulcer or upper GI bleeding within the prior 30 days.
12. Patients with a documented allergy towards contrast media, and to any compound of the investigated medical device.
13. Patients that have neurological disease severely affecting ambulation or day to day functioning.
14. Patients with any stroke within the prior 30 days.
15. Patients with senile dementia, according to the advice from a specialized neurologist.
16. Patients in whom transesophageal echocardiography (TEE) is contraindicated since TEE is used for both preoperative screening and guidance during implant procedure.
17. Patients who is unwilling or deemed by the Investigator to be unwilling to comply with the requirements of the protocol, or subject with a history of non-compliance.
18. Patients unable to understand and sign the Informed Consent Form in absence of legal representative.
19. Patients with a lack of capacity to consent.

20. Patients unable to read and write.

    - Echographic exclusion criteria (preoperative screening)

21. Patients with left ventricular apex aneurysm;
22. Patients with aorto-mitral angle <120°;

23. Patients with a systolic/diastolic mitral valve area assessed as not compatible with the sizing policy matrix defined by the Sponsor.

    - Computerized Tomographic (CT) exclusion criteria (preoperative screening)

24. Patients with ventricular morphology (position of papillary muscles, ventricular wall hypertrophy) unsuitable with the study valve design;
25. Patients with aorto-mitral angle <120°;
26. Patients with a systolic/diastolic mitral valve area assessed as not compatible with the sizing policy matrix defined by the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Implanted patients; Implantation of Epygon mitral valve prosthesis	Device: Epygon™ Transcatheter Mitral Valve System; The EPYGON VALVE is an innovative mitral valve, intended for valve replacement of a native mitral valve through a minimally invasive implant procedure by means of a dedicated implant device. The EPYGON VALVE is a bio prosthesis, composed by a functional assembly of bovine pericardium on a NiTinol stent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Safety	defined as the absence of major device or procedure related serious adverse events evaluated on the following clinical events: death; major cardiac structural complications (as per MVARC definitions); life-threatening bleeding (MVARC scale); any prosthesis-related dysfunction, migration, thrombosis, or other complication, that require surgery or repeated intervention.; myocardial infarction or coronary ischemia requiring PCI or CABG; severe hypotension, heart failure or respiratory failure requiring intravenous vasopressors 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; major vascular complications; stroke; stage 2 or 3 acute kidney injury (includes new dialysis)	[Timeframe: at 30 days]
Device Success	Technical Success (as per MVARC definition) defined as alive patient at exit from procedure room, with all of the following:Successful access, delivery and retrieval of the Epygon delivery systemSuccessful deployment and positioning of the Epygon Transcatheter mitral valveFreedom from additional emergency surgery or re-intervention related to the device or access procedure.; Continued intended safety and performance of the device, including:No evidence of structural or functional failure (as per MVARC definition)No specific device-related technical failure issues and complications (as per MVARC definition)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)	[Timeframe: at 30 days]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Safety	defined as absence of major device or procedure related serious adverse events evaluated on the following clinical events: death; major cardiac structural complications; life-threatening bleeding (MVARC scale); any prosthesis-related dysfunction, migration, thrombosis, or other complication, that require surgery or repeated intervention.; myocardial infarction or coronary ischemia requiring PCI or CABG; severe hypotension, heart failure or respiratory failure requiring intravenous vasopressors 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; major access complications; stroke; stage 2 or 3 acute kidney injury (includes new dialysis)	[Time frame: 3, 6, 12 months and yearly up to 5 years from implantation]
Patient success (as per MVARC definition)	All of the following must be present: Device success (either optimal or acceptable); Patient returned to the pre-procedural setting; No rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, heart failure); Improvement from baseline in symptoms (e.g., NYHA improvement by ≥ 1 functional class); Improvement from baseline in functional status (e.g., 6-min walk test improvement by ≥ 50 m); Improvement from baseline in quality-of-life (e.g., Kansas City Cardiomyopathy Questionnaire improvement by ≥ 10)	[Time frame: 12 months from implantation]
Evaluation of clinical status on the basis of the NYHA functional classification		[Time frame Preoperative, 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Six-minute walk test		[Time frame: Preoperative, 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Quality of Life score (Kansas City Cardiomyopathy Questionnaire)	The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	[Time frame: Preoperative, 3, 6, 12 months and yearly up to 5 years from implantation]
Hemodynamic performance assessed by echocardiography	Prosthetic mean atrio-ventricular ΔP < 5 mm Hg; Prosthetic Effective Orifice Area (EOA) ≥ 1.5 cm2; Mitral valve regurgitation reduction (vs. preoperative) of at least 1 grade and not more than moderate (2+); Prosthetic paravalvular valve leakage (PVL) not more than mild (1+) without hemolysis	[Time frame: Preoperative on native mitral valve, Postoperative, 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Device Success	Technical Success (as per MVARC definition) defined as alive patient at exit from procedure room, with all of the following:Successful access, delivery and retrieval of the Epygon delivery systemSuccessful deployment and positioning of the Epygon bioprosthesisFreedom from additional emergency surgery or re-intervention related to the device or access procedure.; Continued intended safety and performance of the device, including:No evidence of structural or functional failure (as per MVARC definition)No specific device-related technical failure issues and complications (as per MVARC definition)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)	[Time frame: 3, 6, 12 months and yearly up to 5 years from implantation]
Procedural Success	All of the following must be present: Device success (either optimal or acceptable), And; Absence of major device or procedure related serious adverse events, including:deathmajor cardiac structural complications (as per MVARC definitions)life-threatening bleeding (MVARC scale)any prosthesis-related dysfunction, migration, thrombosis, or other complication, that require surgery or repeated intervention.myocardial infarction or coronary ischemia requiring PCI or CABGsevere hypotension, heart failure or respiratory failure requiring intravenous vasopressors 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 ≥ 48Hmajor vascular complicationsstrokestage 2 or 3 acute kidney injury (includes new dialysis).	[Time frame: 30 days]
Incidence of adverse events		[Time frame: 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Incidence of serious adverse events		[Time frame: 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Incidence of adverse events related to device		[Time frame: 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Incidence of adverse events related to procedure		[Time frame: 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Absence of all-cause mortality		[Time frame: 30 days, 3, 6, 12 months and yearly up to 5 years from implantation]
Technical Success (as per MVARC definition)	defined as alive patient at exit from procedure room, with all of the following: Successful access, delivery and retrieval of the Epygon delivery system; Successful deployment and positioning of the Epygon Transcatheter mitral valve; Freedom from additional emergency surgery or re-intervention related to the device or access procedure.	[Time Frame: immediately after procedure]

Collaborators and Investigators

• Sponsor: Epygon

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Mitral regurgitation; Mitral valve replacement
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: MINERVA FIH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No