A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation (RESHAPE-HF)

This study has been terminated.
(As recruitment rate was lower than anticipated)
Sponsor:
Collaborator:
Abbott Vascular
Information provided by (Responsible Party):
Evalve
ClinicalTrials.gov Identifier:
NCT01772108
First received: January 17, 2013
Last updated: January 6, 2015
Last verified: January 2015
  Purpose

This trial is a randomized study of the MitraClip device in heart failure patients with clinically significant functional mitral regurgitation. A hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations is hypothesized to occur at a lower rate with the use of the MitraClip device in addition to optimal standard medical therapy compared to optimal standard of care therapy alone.


Condition Intervention
Cardiovascular Diseases
Device: MitraClip

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation

Resource links provided by NLM:


Further study details as provided by Evalve:

Primary Outcome Measures:
  • Hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    The analysis will be carried out when the last patient completes 12-month follow-up. All follow-up, up to 24 months, will be included in the analysis.


Secondary Outcome Measures:
  • Composite of all-cause mortality, stroke, myocardial infarction, new need for renal replacement therapy, and non-elective cardiovascular surgery for device related complications in the Device group at 30 days [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Mitral regurgitation severity reduction to mild or mild-to-moderate at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in Left Ventricular End Diastolic Volume (LVEDV) at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in Left Ventricular End Systolic Volume (LVESV) at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in 6 Minute Walk Test (6MWT) distance at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in Quality of Life (QoL) score, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ), at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • New York Heart Association (NYHA) Functional Class I/II at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: April 2013
Estimated Study Completion Date: January 2015
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MitraClip Device
Subjects randomized to the Device group will undergo the MitraClip procedure in addition to optimal standard medical therapy
Device: MitraClip
The MitraClip System includes a MitraClip device, a Steerable Guide Catheter, and a MitraClip Delivery System that enables placement of the MitraClip device on the mitral valve leaflets
No Intervention: Control
Subjects randomized to the Control group will receive optimal standard of care therapy alone

Detailed Description:

This study is a clinical evaluation of the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with chronic heart failure. The objective is to further study the safety and effectiveness of the MitraClip System for the treatment of clinically significant functional mitral regurgitation in New York Heart Association Functional Class III or IV chronic heart failure patients.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 years and 90 years old
  • Clinically significant functional mitral regurgitation (moderate-to-severe or severe mitral regurgitation), as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory
  • Assessed by the investigator to be on optimal standard of care therapy for heart failure for at least 4 weeks with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization
  • Documented New York Heart Association Class III or Class IV heart failure, despite optimal standard of care therapy, within 90 days preceding randomization
  • Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of at least 350 pg/mL for BNP or at least 1400 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization
  • Left ventricular ejection fraction (LVEF) ≥15% and ≤40% determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory
  • Left ventricular end diastolic diameter (LVEDD) ≥55 mm determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory
  • Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness
  • Subject agrees to return for all required post-procedure follow-up visits
  • The subject has been informed of the nature of the study and agrees to the study's provisions, including the possibility of randomization to the Control group, and has provided written informed consent as approved by the respective clinical site's Ethics Committee

Exclusion Criteria:

  • Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative mitral regurgitation), as determined by transesophageal echocardiography
  • Status 1 heart transplant or prior orthotopic heart transplantation
  • Introduction of a new heart failure drug class within the last 4 weeks prior to randomization
  • Cardiovascular hospitalization within the last 2 weeks immediately prior to randomization
  • Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization
  • Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery or atrial fibrillation ablation within 90 days prior to randomization
  • Implant of any rhythm management device (i.e., pacemaker, Cardiac Resynchronization Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD) within 90 days prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization
  • Need for any cardiovascular surgery
  • Mitral valve surgery is considered a therapeutic option for the subject
  • Renal replacement therapy
  • Uncontrolled hypertension (i.e., BP >180 mmHg systolic and/or >105 mmHg diastolic) or hypotension (i.e., BP <90 mmHg systolic)
  • Unstable angina pectoris as judged by the investigator, other clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias
  • 6MWT distance >450 meters
  • Mitral Valve Area (MVA) by planimetry <4.0 cm2; if MVA by planimetry is not measurable, pressure half-time measurement is acceptable; MVA must be confirmed by the Echocardiography Core Laboratory
  • Leaflet anatomy which may preclude MitraClip device implantation, proper device positioning on the leaflets, or sufficient reduction in mitral regurgitation that may include:

    • Evidence of calcification in the grasping area
    • Presence of significant cleft in the grasping area
    • Lack of both primary and secondary chordal support in the grasping area
    • Prior mitral valve surgery
    • Coaptation length ≤2 mm
    • Leaflet mobility length <1 cm
  • Presence of an IVC filter in the femoral vein that would interfere with the delivery catheter, or ipsilateral deep vein thrombosis (DVT) is present
  • Contraindication to transseptal catheterization
  • Subjects in whom transesophageal echocardiography is contraindicated
  • Echocardiographic evidence of intracardiac mass, thrombus, or vegetation
  • Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated)
  • Presence of any of the following:

    • Severe aortic stenosis (aortic valve area <1.0 cm2) or severe aortic regurgitation
    • Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis)
    • 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
    • Hemodynamic instability requiring inotropic support or mechanical heart circulatory support
  • Active infections requiring current antibiotic therapy
  • Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically
  • Severe right ventricular failure or severe tricuspid regurgitation
  • History of bleeding diathesis or coagulopathy or subject who refuses blood transfusions
  • Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to randomization and be adherent to an accepted method of contraception
  • Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the investigator
  • Currently participating in another therapeutic or interventional heart failure trial, or in any trial of an unapproved drug or device (Subjects participating in observational studies or registries may be considered as eligible)
  • Subject belongs to a vulnerable population per investigator's judgment or subject has any kind of disorder that compromises his/her ability to give written informed consent and/or to comply with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772108

Locations
Austria
Allgemein öffentliches Krankenhaus Elisabethinen Linz
Linz, Fadingerstraße 1, Austria, A-4020
Belgium
UZA
Edegem, Belgium
Denmark
Skejby Sykehus/Aarhus University Hospital
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark
Odense Universitetshospital
Odense, Denmark
Finland
Helsinski University Hospital
Helsinski, Finland
Germany
Universitätsklinikum der RWTH - Aachen
Aachen, Germany
Herz-Zentrum
Bad Krozingen, Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany
Evangelish-Freikirchliches Krankenhaus, Bernau
Bernau, Germany
Herzzentrum Göttingen Universitätsmedizin, Göttingen
Göttingen, Germany
Asklepios Klinik St Georg, Hamburg
Hamburg, Germany
Kardiologische Gemeinschaftspraxis Mathey-Schofer, Hamburg
Hamburg, Germany
Universitäre Herzzentrum, Hamburg
Hamburg, Germany
Uni-Klinikum Heidelberg
Heidelberg, Germany
Johannes Gütenberg University, Mainz
Mainz, Germany
Italy
Spedali Civili di Brescia
Brescia, Italy
Ospedale Ferrarotto Alessi, Catania
Catania, Italy
Ospedale San Raffaele, Milano
Milano, Italy
Centro Cardiologico Monzino
Monzino, Italy
Azienda Ospedaliero Universitaria Pisana, Pisa
Pisa, Italy
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
St Antonius Ziekenhuis, Nieuwegein
Nieuwegein, Netherlands
Spain
Hospital Sant Creu y Sant Pau,
Barcelona, Spain
Sweden
Karolinska University Hospital, Stockholm
Stockholm, Sweden
Switzerland
Universitätsspital Basel
Basel, Switzerland
Inselspital Bern
Bern, Switzerland
Universitäts Spital Zürich
Zürich, Switzerland
Sponsors and Collaborators
Evalve
Abbott Vascular
Investigators
Principal Investigator: Piotr Ponikowski, MD, PhD Military Hospital, Medical University, Wroclaw, Poland
  More Information

Publications:
Zannad F. Acute heart failure syndromes: the 'Cinderella' of heart failure research. European Journal Supplements. 2005 April 7;(suppl B):B8-B127.
Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC Committee for Practice Guidelines (CPG). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008 Oct;29(19):2388-442. doi: 10.1093/eurheartj/ehn309. Epub 2008 Sep 17. Review. Erratum in: Eur Heart J. 2010 Apr;12(4):416. Dosage error in article text. Eur Heart J. 2010 Mar;31(5):624. Dosage error in article text.
Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. doi: 10.1016/j.jacc.2008.05.007.
Nishimura RA, Carabello BA, Faxon DP, Freed MD, Lytle BW, O'Gara PT, O'Rourke RA, Shah PM, Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC Jr, Jacobs AK, Buller CE, Creager MA, Ettinger SM, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Page RL, Tarkington LG, Yancy CW Jr; American College of Cardiology/American Heart Association Task Force. ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008 Aug 19;118(8):887-96. doi: 10.1161/CIRCULATIONAHA.108.190377. Epub 2008 Jul 28.
Efron B, Tibshirani RJ. An Introduction to the Bootstrap. 1993. Chapman & Hall: New York. EuroQoL Group. The EuroQol - a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24.

Responsible Party: Evalve
ClinicalTrials.gov Identifier: NCT01772108     History of Changes
Other Study ID Numbers: 12-513
Study First Received: January 17, 2013
Last Updated: January 6, 2015
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Evalve:
Heart Valve Diseases

Additional relevant MeSH terms:
Mitral Valve Insufficiency
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases

ClinicalTrials.gov processed this record on March 30, 2015