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Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair (PRE-MITRA)

Primary Purpose

Severe Mitral Regurgitation

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Cardiac magnetic resonance imaging before the procedure
Transcatheter mitral edge-to-edge repair.
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Severe Mitral Regurgitation focused on measuring Cardiac magnet resonance (CMR), Mitral Regurgitation, Transcatheter mitral edge-to-edge repair, MitraClip, CMR feature tracking, Parametric mapping

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with severe secondary MR characterized, according to the European guidelines and recommendations, by a regurgitant volume ≥30 mL/beat or an effective regurgitant orifice ≥20 mm².
  • Symptomatic patients with New York Heart Association Class ≥II.
  • Left ventricular ejection fraction between 15% and 50%.
  • Optimal standard of care therapy for heart failure according to investigator.
  • Not eligible for a mitral surgery intervention according to the Heart Team.
  • Patients who have the ability to understand the requirements of the study and provide written consent/assent to participate and agree to abide by the study requirements.

Exclusion Criteria:

  • Participants younger than 18 years
  • Pregnancy or breastfeeding
  • Severe impaired renal function (GFR < 15 ml/min)
  • Patients with untreated severe concomitant valve disease (e.g. severe tricuspid valve regurgitation, aortic stenosis)
  • The patient has a medical condition, serious concurrent illness, or extenuating circumstance that would significantly decrease study compliance, including all prescribed follow-up
  • The patient has contraindications to CMR, including: Implanted non-CMR conditional metallic implants, pacemaker, intracardiac defibrillator, neurostimulator, epicardial pacemaker leads, or any abandoned leads, ferromagnetic aneurysm clip, ferromagnetic halo device, cochlear implants, implanted infusion pumps or severe claustrophobia
  • The patient is clinically unstable or has stage D congestive heart failure or inability to lay flat for 60 minutes

Sites / Locations

  • Department of Cardiology, University Hospital Bern, Inselspital, BernRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

Patients undergoing transcatheter mitral edge-to-edge repair in this single-arm study.

Outcomes

Primary Outcome Measures

Rate of patients with reverse remodeling after 12 months
Defined as ≥10% reduction in left ventricular end-diastolic volume in patients with successful MR reduction to grade 2+ or less 12 months after mitral edge-to-edge repair assessed by echocardiography.

Secondary Outcome Measures

Rate of patients with procedural and device success
Procedural and device success as defined according to the criteria of the Mitral Valve Academic Research Consortium
Rate of patients with reverse remodeling after 6 and 24 months
Reverse remodeling at 6 and 24 months, defined according to previously mentioned criteria.
Change of left ventricular sphericity index
Echocardiographic assessment of LV sphericity index measured using the LV short/long axis dimension ratio in the end-diastolic four-chamber apical view.
Change in NT-proBNP levels
Change in NT-proBNP levels as an indirect sign of changes in left ventricular filling pressure, fibrosis and reverse remodeling will be measured in clinically indicated follow-ups at different time points after the intervention.
All cause death
Occurence of death from any cause
Cardiovascular death
Occurence of death from cardiovascular reason
Rate of patients with heart-failure related hospitalization
Hospitalizations for heart failure within the observation time will be systematically recorded.
Change in NYHA class
Change in NYHA class ≥ +/- 1 compared to baseline NYHA-class before mitral edge-to-edge repair.
Change in myocardial strain
Clinically indicated follow-up imaging (CMR) will be analyzed by CMR feature tracking
Change in left ventricular ejection fraction
Echocardiographic assessment of left ventricular ejection fraction measured according to biplane Simpson disk summation method.

Full Information

First Posted
May 27, 2021
Last Updated
November 1, 2022
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University Hospital, Basel, Switzerland, Cardiocentro Ticino, Triemli Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04913727
Brief Title
Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair
Acronym
PRE-MITRA
Official Title
Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University Hospital, Basel, Switzerland, Cardiocentro Ticino, Triemli Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators' hypothesis is that CMR tissue characterization and myocardial function analysis acquired by CMR feature tracking technique predict reverse remodeling in patients with severe secondary mitral regurgitation (MR) undergoing transcatheter mitral edge-to-edge repair.
Detailed Description
Diametrically opposed results of the COAPT- and the MITRA-FR trial have demonstrated the need for additional evidence in the field of transcatheter mitral edge-to-edge repair. Reverse left ventricular remodeling after treatment of severe secondary mitral regurgitation can indicate treatment response and is associated with positive outcomes. However, so far it is reverse remodeling, respectively treatment response is difficult to predict, which complicates patient selection for mitral edge-to-edge repair. Previous studies have shown, that focal (late gadolinium enhancement (LGE)) but not diffuse myocardial fibrosis (T1 mapping and extracellular volume fraction (ECV)) burden quantification using CMR predicts reverse left ventricular remodeling following cardiac resynchronization therapy in patients with heart failure with reduced ejection fraction (HFrEF). On the other hand, myocardial T1 mapping was predictive for beneficial left ventricular remodeling after long-term heart failure therapy. Furthermore, in patients with HFrEF, LGE is associated with clinical outcome and an incremental predictive value to left ventricular dimensions and function. However, as only 1/3 of HFrEF patients show LGE, subtle fibrosis might be missed. Recently the investigators have shown that different novel fibrosis detection techniques (naive T1 mapping, mean ECV and λGd being the delta of pre- and post T1 mapping and ECV calculation) all demonstrated strong association with outcome in patients with heart failure. The investigators' hypothesis is that these markers (CMR tissue characterization and myocardial function analysis acquired by a CMR feature tracking) might also be helpful in predicting reverse remodeling after transcatheter mitral edge-to-edge repair. This project might help to understand the pathophysiology of the disease in patients with secondary mitral regurgitation, improve risk stratification in this clinical setting, and optimize selection of patients who benefit from transcatheter mitral edge-to-edge repair.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Mitral Regurgitation
Keywords
Cardiac magnet resonance (CMR), Mitral Regurgitation, Transcatheter mitral edge-to-edge repair, MitraClip, CMR feature tracking, Parametric mapping

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Patients undergoing transcatheter mitral edge-to-edge repair in this single-arm study.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cardiac magnetic resonance imaging before the procedure
Intervention Description
CMR image acquisition with previously mentioned analysis
Intervention Type
Procedure
Intervention Name(s)
Transcatheter mitral edge-to-edge repair.
Intervention Description
Included patients will undergo Transcatheter mitral edge-to-edge repair.
Primary Outcome Measure Information:
Title
Rate of patients with reverse remodeling after 12 months
Description
Defined as ≥10% reduction in left ventricular end-diastolic volume in patients with successful MR reduction to grade 2+ or less 12 months after mitral edge-to-edge repair assessed by echocardiography.
Time Frame
12 months after mitral edge-to-edge repair
Secondary Outcome Measure Information:
Title
Rate of patients with procedural and device success
Description
Procedural and device success as defined according to the criteria of the Mitral Valve Academic Research Consortium
Time Frame
24 months after mitral edge-to-edge repair
Title
Rate of patients with reverse remodeling after 6 and 24 months
Description
Reverse remodeling at 6 and 24 months, defined according to previously mentioned criteria.
Time Frame
6 and 24 months after mitral edge-to-edge repair
Title
Change of left ventricular sphericity index
Description
Echocardiographic assessment of LV sphericity index measured using the LV short/long axis dimension ratio in the end-diastolic four-chamber apical view.
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
Change in NT-proBNP levels
Description
Change in NT-proBNP levels as an indirect sign of changes in left ventricular filling pressure, fibrosis and reverse remodeling will be measured in clinically indicated follow-ups at different time points after the intervention.
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
All cause death
Description
Occurence of death from any cause
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
Cardiovascular death
Description
Occurence of death from cardiovascular reason
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
Rate of patients with heart-failure related hospitalization
Description
Hospitalizations for heart failure within the observation time will be systematically recorded.
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
Change in NYHA class
Description
Change in NYHA class ≥ +/- 1 compared to baseline NYHA-class before mitral edge-to-edge repair.
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair
Title
Change in myocardial strain
Description
Clinically indicated follow-up imaging (CMR) will be analyzed by CMR feature tracking
Time Frame
Within 24 months after mitral edge-to-edge repair
Title
Change in left ventricular ejection fraction
Description
Echocardiographic assessment of left ventricular ejection fraction measured according to biplane Simpson disk summation method.
Time Frame
6, 12 and 24 months after mitral edge-to-edge repair

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with severe secondary MR characterized, according to the European guidelines and recommendations, by a regurgitant volume ≥30 mL/beat or an effective regurgitant orifice ≥20 mm². Symptomatic patients with New York Heart Association Class ≥II. Left ventricular ejection fraction between 15% and 50%. Optimal standard of care therapy for heart failure according to investigator. Not eligible for a mitral surgery intervention according to the Heart Team. Patients who have the ability to understand the requirements of the study and provide written consent/assent to participate and agree to abide by the study requirements. Exclusion Criteria: Participants younger than 18 years Pregnancy or breastfeeding Severe impaired renal function (GFR < 15 ml/min) Patients with untreated severe concomitant valve disease (e.g. severe tricuspid valve regurgitation, aortic stenosis) The patient has a medical condition, serious concurrent illness, or extenuating circumstance that would significantly decrease study compliance, including all prescribed follow-up The patient has contraindications to CMR, including: Implanted non-CMR conditional metallic implants, pacemaker, intracardiac defibrillator, neurostimulator, epicardial pacemaker leads, or any abandoned leads, ferromagnetic aneurysm clip, ferromagnetic halo device, cochlear implants, implanted infusion pumps or severe claustrophobia The patient is clinically unstable or has stage D congestive heart failure or inability to lay flat for 60 minutes
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christoph MD Gräni, PHD
Phone
+41 31 632 4508
Email
christoph.graeni@insel.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoph MD Gräni, PHD
Organizational Affiliation
Department of Cardiology, University Hospital Bern, Inselspital, Bern
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology, University Hospital Bern, Inselspital, Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Gräni, Prof
Phone
+41316324508
Email
christoph.graeni@insel.ch

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30280640
Citation
Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Weissman NJ, Mack MJ; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23.
Results Reference
result
PubMed Identifier
30145927
Citation
Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, Lefevre T, Piot C, Rouleau F, Carrie D, Nejjari M, Ohlmann P, Leclercq F, Saint Etienne C, Teiger E, Leroux L, Karam N, Michel N, Gilard M, Donal E, Trochu JN, Cormier B, Armoiry X, Boutitie F, Maucort-Boulch D, Barnel C, Samson G, Guerin P, Vahanian A, Mewton N; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018 Dec 13;379(24):2297-2306. doi: 10.1056/NEJMoa1805374. Epub 2018 Aug 27.
Results Reference
result
PubMed Identifier
31005977
Citation
Praz F, Grasso C, Taramasso M, Baumbach A, Piazza N, Tamburino C, Windecker S, Maisano F, Prendergast B. Mitral regurgitation in heart failure: time for a rethink. Eur Heart J. 2019 Jul 14;40(27):2189-2193. doi: 10.1093/eurheartj/ehz222. No abstract available.
Results Reference
result
PubMed Identifier
29025553
Citation
Grani C, Eichhorn C, Biere L, Murthy VL, Agarwal V, Kaneko K, Cuddy S, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis. J Am Coll Cardiol. 2017 Oct 17;70(16):1964-1976. doi: 10.1016/j.jacc.2017.08.050. Erratum In: J Am Coll Cardiol. 2017 Nov 28;70(21):2736.
Results Reference
result
PubMed Identifier
30756221
Citation
Grani C, Biere L, Eichhorn C, Kaneko K, Agarwal V, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis. Int J Cardiovasc Imaging. 2019 Jun;35(6):1067-1078. doi: 10.1007/s10554-019-01552-6. Epub 2019 Feb 12.
Results Reference
result
PubMed Identifier
30813942
Citation
Grani C, Eichhorn C, Biere L, Kaneko K, Murthy VL, Agarwal V, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis. J Cardiovasc Magn Reson. 2019 Feb 28;21(1):14. doi: 10.1186/s12968-019-0520-0.
Results Reference
result

Learn more about this trial

Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair

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