AHEAD: European Feasibility Study of the Cardiovalve Transfemoral Mitral Valve System (AHEAD)
Primary Purpose
Mitral Regurgitation, Mitral Valve Disease
Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Cardiovalve Transfemoral Mitral Valve
Sponsored by
About this trial
This is an interventional treatment trial for Mitral Regurgitation focused on measuring Mitral Insufficiency, Heart Failure, Mitral Valve, Heart Diseases, Valvular Heart Disease
Eligibility Criteria
General Inclusion Criteria
- Age ≥ 18 years
- NYHA functional II, III or ambulatory IV
- Severe mitral regurgitation (MR grade 3-4+)
- Subject is on optimal guideline-directed medical therapy for heart failure for at least 30 days or CRT if indicated.
- 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.
- Able to undergo Transesophageal Echocardiography (TEE).
- Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed.
The subject commits to return for the scheduled post-operative follow-up visits at the hospital.
Anatomical Inclusion Criteria
- Suitable for femoral access procedure and trans septal catheterization
- 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
- 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
Sites / Locations
- Universitätsklinikum BonnRecruiting
- Herzzentrum der Uniklinik Köln
- Studienzentrale der Medizinische Klinik II Universitäres Herzzentrum LübeckRecruiting
- Universitaet_Mainz
- Klinikum der Universität München LMURecruiting
- HygeaRecruiting
- Maria Cecilia HospitalRecruiting
- Fondazione Toscana G. Monasterio-Ospedale del CuoreRecruiting
- San Raffaele HospitalRecruiting
- Policlinico San DonatoRecruiting
- A.O.U. PisanaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cardiovalve Transfemoral Mitral Valve
Arm Description
Mitral replacement valve delivered through a transfemoral access and transseptal approach
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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]
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
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
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)
Full Information
NCT ID
NCT03339115
First Posted
November 7, 2017
Last Updated
July 28, 2022
Sponsor
Cardiovalve Ltd.
Collaborators
Meditrial Europe Ltd., Meditrial SrL
1. Study Identification
Unique Protocol Identification Number
NCT03339115
Brief Title
AHEAD: European Feasibility Study of the Cardiovalve Transfemoral Mitral Valve System
Acronym
AHEAD
Official Title
European Feasibility Study of High Surgical Risk Patients With Severe Mitral Regurgitation Treated With the Cardiovalve Transfemoral Mitral Valve System (AHEAD Study)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 23, 2018 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cardiovalve Ltd.
Collaborators
Meditrial Europe Ltd., Meditrial SrL
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitral Regurgitation, Mitral Valve Disease
Keywords
Mitral Insufficiency, Heart Failure, Mitral Valve, Heart Diseases, Valvular Heart Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cardiovalve Transfemoral Mitral Valve
Arm Type
Experimental
Arm Description
Mitral replacement valve delivered through a transfemoral access and transseptal approach
Intervention Type
Device
Intervention Name(s)
Cardiovalve Transfemoral Mitral Valve
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary safety endpoint is freedom from all-cause mortality and major adverse events
Description
Freedom from all-cause mortality, all cause hospitalization, major adverse cardiac events (MACE), major device- or procedure- related serious adverse events
Time Frame
30 days, 3 Months, 6 Months, 12 Months, and 24 Months
Secondary Outcome Measure Information:
Title
Technical success
Description
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]
Time Frame
Intraoperative, 30 Days
Title
Device Success
Description
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
Time Frame
Intraoperative
Title
Device Success
Description
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
Time Frame
30 days, 3 Months, 6 Months, 12 Months, and 24 Months
Title
Patient Success
Description
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)
Time Frame
30 days, 3 Months, 6 Months, 12 Months, and 24 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
General Inclusion Criteria
Age ≥ 18 years
NYHA functional II, III or ambulatory IV
Severe mitral regurgitation (MR grade 3-4+)
Subject is on optimal guideline-directed medical therapy for heart failure for at least 30 days or CRT if indicated.
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.
Able to undergo Transesophageal Echocardiography (TEE).
Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed.
The subject commits to return for the scheduled post-operative follow-up visits at the hospital.
Anatomical Inclusion Criteria
Suitable for femoral access procedure and trans septal catheterization
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nitza Shoham, VP CA&A
Phone
+972765388142
Email
nitza@cardiovalve.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Beker, PhD
Email
lbaker@boston-biomedical.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nitza Shoham, VP CA&RA
Organizational Affiliation
Cardiovalve Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum Bonn
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georg Nickenig, MD
Phone
+4922828715217
Email
georg.nickenig@ukbonn.de
First Name & Middle Initial & Last Name & Degree
Georg Nickenig, MD
First Name & Middle Initial & Last Name & Degree
Nikos Werner, MD
First Name & Middle Initial & Last Name & Degree
Jan-Malte Sinning, MD
First Name & Middle Initial & Last Name & Degree
Marcel Weber, MD
Facility Name
Herzzentrum der Uniklinik Köln
City
Köln
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan Baldus, MD
Phone
+49 221 478 32511
Email
stephan.baldus@uk-koeln.de
First Name & Middle Initial & Last Name & Degree
Stephan Baldus, MD
Facility Name
Studienzentrale der Medizinische Klinik II Universitäres Herzzentrum Lübeck
City
Lübeck
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Frerker
Phone
0451 500-44501
Email
christian.frerker@uksh.de
Facility Name
Universitaet_Mainz
City
Mainz
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan von Bardeleben, MD
First Name & Middle Initial & Last Name & Degree
Tobias Ruf, MD
Email
Tobias.Ruf@unimedizin-mainz.de
Facility Name
Klinikum der Universität München LMU
City
München
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jörg Hausleiter, MD
Phone
+49 89 4400 72361
Email
joerg.hausleiter@med.uni-münchen.de
First Name & Middle Initial & Last Name & Degree
Jörg Hausleiter, MD
Facility Name
Hygea
City
Athens
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Konstantinos Spargias
Email
kspargias@yahoo.com
Facility Name
Maria Cecilia Hospital
City
Cotignola
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Colombo, MD
Facility Name
Fondazione Toscana G. Monasterio-Ospedale del Cuore
City
Massa
ZIP/Postal Code
54100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sergio Berti, Dr.
Facility Name
San Raffaele Hospital
City
Milano
ZIP/Postal Code
20129
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Denti, Dr.
Email
denti.paolo@hsr.it
Facility Name
Policlinico San Donato
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Bedogni, MD
Phone
+39 02 5277 4570
Email
francesco.bedogni@grupposandonato.it
Facility Name
A.O.U. Pisana
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna S Petronio, Dr.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
AHEAD: European Feasibility Study of the Cardiovalve Transfemoral Mitral Valve System
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