AHEAD: European Feasibility Study of the Cardiovalve Transfemoral Mitral Valve System (AHEAD)

European Feasibility Study of High Surgical Risk Patients With Severe Mitral Regurgitation Treated With the Cardiovalve Transfemoral Mitral Valve System (AHEAD Study)

This study will evaluate the safety of the Cardiovalve Transfemoral Mitral Valve System with its associated procedure, and observe the device performance in reducing mitral regurgitation. Data collected in this clinical study will include 30-day safety and performance, and long-term clinical outcomes over a follow-up of 2 years.

Study Overview

• Status: Recruiting
• Conditions: Mitral Regurgitation; Mitral Valve Disease
• Intervention / Treatment: Device: Cardiovalve Transfemoral Mitral Valve

Detailed Description

The Cardiovalve offers a mitral replacement valve delivered through a transfemoral access and transseptal approach, and is intended to reduce mortality and adverse event rates in selected patients for whom surgical options are not feasible.

Innovation: A truly trans femoral, trans venous delivery of the prosthetic mitral valve which minimizes procedural risk. The Cardiovalve Implant features a dual nitinol frame for robust radial strength with decoupling of the atrial flange and ventricular portion which contains 24 grasping legs designed for atraumatic anchoring of the device to the native mitral annulus. Valve leaflets are made of bovine pericardium. The Cardiovalve implant has a very low left ventricle (LV) protrusion footprint thus reducing the risk of LV outflow tract obstruction and/or interference with the LV. The Cardiovalve delivery system (DS) is designed for transfemoral delivery of the Implant with transseptal access to the left atrium. The catheter assembly is used to center the implant relative to the native mitral valve plane and align it with the left ventricual apex-to-base axis. After valve implantation, the delivery system is withdrawn.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nitza Shoham, VP CA&A; Phone Number: +972765388142; Email: nitza@cardiovalve.com
• Study Contact Backup: Name: Lauren Beker, PhD; Email: lbaker@boston-biomedical.com

Study Locations

• Germany
  • Köln, Germany
    • Not yet recruiting
    • Herzzentrum der Uniklinik Köln
    • Contact: Stephan Baldus, MD; Phone Number: +49 221 478 32511; Email: stephan.baldus@uk-koeln.de
    • Principal Investigator: Stephan Baldus, MD
  • Lübeck, Germany
    • Recruiting
    • Studienzentrale der Medizinische Klinik II Universitäres Herzzentrum Lübeck
    • Contact: Christian Frerker; Phone Number: 0451 500-44501; Email: christian.frerker@uksh.de
  • Mainz, Germany
    • Not yet recruiting
    • Universitaet_Mainz
    • Contact: Tobias Ruf, MD; Email: Tobias.Ruf@unimedizin-mainz.de
    • Contact: Stephan von Bardeleben, MD
  • München, Germany
    • Recruiting
    • Klinikum der Universität München LMU
    • Contact: Jörg Hausleiter, MD; Phone Number: +49 89 4400 72361; Email: joerg.hausleiter@med.uni-münchen.de
    • Principal Investigator: Jörg Hausleiter, MD
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53127
      • Recruiting
      • Universitätsklinikum Bonn
      • Sub-Investigator: Nikos Werner, MD
      • Sub-Investigator: Jan-Malte Sinning, MD
      • Sub-Investigator: Marcel Weber, MD
      • Contact: Georg Nickenig, MD; Phone Number: +4922828715217; Email: georg.nickenig@ukbonn.de
      • Principal Investigator: Georg Nickenig, MD
• Greece
  • Athens, Greece
    • Recruiting
    • Hygea
    • Contact: Konstantinos Spargias; Email: kspargias@yahoo.com
• Italy
  • Cotignola, Italy
    • Recruiting
    • Maria Cecilia Hospital
    • Contact: Antonio Colombo, MD
  • Massa, Italy, 54100
    • Recruiting
    • Fondazione Toscana G. Monasterio-Ospedale del Cuore
    • Contact: Sergio Berti, Dr.
  • Milano, Italy, 20129
    • Recruiting
    • San Raffaele Hospital
    • Contact: Paolo Denti, Dr.; Email: denti.paolo@hsr.it
  • Milano, Italy
    • Recruiting
    • Policlínico San Donato
    • Contact: Francesco Bedogni, MD; Phone Number: +39 02 5277 4570; Email: francesco.bedogni@grupposandonato.it
  • Pisa, Italy, 56126
    • Recruiting
    • A.O.U. Pisana
    • Contact: Anna S Petronio, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria

1. Age ≥ 18 years
2. NYHA functional II, III or ambulatory IV
3. Severe mitral regurgitation (MR grade 3-4+)
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)

Cardiovascular Exclusion Criteria

1. Prior stroke or TIA within 3 months or Modified Rankin Scale ≥4 disability
2. Acute myocardial infarction within the previous 30 days
3. Any prior heart valve surgery or transcatheter mitral intervention
4. Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days
5. Rheumatic heart disease or endocarditis within the previous 3 months
6. 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
7. Existence of inferior vena cava filter or atrial septal device (contraindicating femoral access and transseptal catheterization)
8. Untreated clinically significant coronary artery disease requiring revascularization
9. Tricuspid valve disease requiring surgery or severe tricuspid regurgitation
10. Aortic or pulmonic valve disease requiring surgery

11. CRT/ICD implant within 30 days

    Anatomical Exclusion Criteria (assessed by pre-procedural imaging)

12. Left Ventricular Ejection Fraction (LVEF) <30%
13. LV end diastolic diameter > 70mm
14. Significant abnormalities of the mitral valve and sub-valvular apparatus.
15. Severe mitral annular or leaflets calcification
16. Left atrial or LV thrombus or vegetation
17. Severe right ventricular dysfunction

18. Severe tricuspid or aortic valve disease

    General Exclusion Criteria

19. Subject who is currently participating in an investigational study, other than this study
20. 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
21. 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
22. Bleeding diathesis or hypercoagulable state
23. Active peptic ulcer or active gastrointestinal bleeding
24. Pulmonary artery systolic pressure >70 mmHg
25. Patients with renal insufficiency (creatinine > 2.5 mg/dL)
26. Need for emergent or urgent surgery for any reason or any planned cardiac Surgery within the next 12 months
27. Subject with hepatic insufficiency
28. Subject has a co-morbid illness that may result in a life expectancy of less than one year
29. Active infection that requires antibiotic therapy
30. Subject is pregnant, breastfeeding or intend to become pregnant within one year

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: Cardiovalve Transfemoral Mitral Valve; Mitral replacement valve delivered through a transfemoral access and transseptal approach	Device: Cardiovalve Transfemoral Mitral Valve; The Cardiovalve Transfemoral Mitral Valve System is intended for use symptomatic patients with severe mitral regurgitation who are at elevated risk for surgical mitral valve repair or replacement and who are anatomically eligible for transfemoral mitral valve replacement with transseptal access to the left atrium.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary safety endpoint is freedom from all-cause mortality and major adverse events	Freedom from all-cause mortality, all cause hospitalization, major adverse cardiac events (MACE), major device- or procedure- related serious adverse events	30 days, 3 Months, 6 Months, 12 Months, and 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	Technical success: I. Absence of procedural mortality II. Delivery and deployment of the device in the correct position and retrieval of delivery catheter, without significant mitral stenosis, LVOT obstruction or paravalvular MR documented by intraoperative imaging [Time Frame:Intraoperative] III. Freedom from emergency surgery or reintervention related to the device or access procedure [Time Frame: 30 days]	Intraoperative, 30 Days
Device Success	I. Absence of procedural mortality or stroke II. Proper placement and positioning of the device III. Freedom from unplanned surgical or interventional procedures related to the device or access procedure	Intraoperative
Device Success	IV. Continued intended safety and performance of the device including: No evidence of structural or functional failure; No specific device-related technical failure issues and complications; 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 Months, 6 Months, 12 Months, and 24 Months
Patient Success	I. Device success (either optimal or acceptable) II. Patient returned to the pre-procedural setting; III. Freedom from rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, worsening of heart failure); IV. Improvement from baseline in NYHA functional class Number of patients with improvement in NYHA class; V. Six minute walk test Increase in distance (m) from baseline; VI. Improvement from baseline in quality-of-life (Kansas City Cardiomyopathy Questionnaire improvement by ≥ 10)	30 days, 3 Months, 6 Months, 12 Months, and 24 Months

Collaborators and Investigators

• Sponsor: Cardiovalve Ltd.
• Collaborators: Meditrial Europe Ltd.; Meditrial SrL
• Investigators: Study Director: Nitza Shoham, VP CA&RA, Cardiovalve Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Mitral Insufficiency; Mitral Valve; Heart Diseases; Valvular Heart Disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: CP 17-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No