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MILLENNIAL: Edge-to-edge Mitral Valve Repair in ATTR-CM

Sponsor
Medical University of Vienna (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06075823
Collaborator
(none)
100
Enrollment
2
Arms
59.4
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

No previous study has evaluated the effectiveness of transcatheter edge-to-edge mitral valve repair (TEER) in patients with ATTR-associated cardiomyopathy (ATTR-CM) and significant mitral regurgitation, as this specific patient population was specifically excluded from previous large TEER trials. From a pathophysiological perspective, effective treatment of significant regurgitant volume and consecutive improvement of forward volume appears highly desirable in a condition with intrinsically low output. However, whether this translates into improved functional capacity, better quality of life, and better clinical outcomes compared to conservative heart failure management alone remains to be investigated.

Condition or Disease Intervention/Treatment Phase
  • Device: TEER
  • Other: Optimal Medical Therapy
 N/A

Detailed Description

It is the aim of this trial to investigate the effectiveness of TEER therapy in patients with proven ATTR-CM and concomitant significant MR as compared to medical therapy alone. Effectiveness will be tested via hard clinical outcomes, biomarkers, functional capacity, and quality of life.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effectiveness and Safety of Edge-to-edge MItral vaLve Repair in Patients With Severe mitraL rEgurgitatioN aNd cardIac ATTR amyLoidosis
Anticipated Study Start Date :
Jan 1, 2024
Anticipated Primary Completion Date :
Dec 12, 2027
Anticipated Study Completion Date :
Dec 12, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Interventional

TEER + Optimal Medical Therapy

Device: TEER
transcatheter edge-to-edge mitral valve repair for significant mitral regurgitation

Other: Optimal Medical Therapy
optimal heart failure management of ATTR-CM
Active Comparator: Control

Optimal Medical Therapy alone

Other: Optimal Medical Therapy
optimal heart failure management of ATTR-CM

Outcome Measures

Primary Outcome Measures

  1. A hierarchical combination of all-cause mortality, cumulative frequency of cardiovascular-related hospitalization, change from baseline in NT-proBNP, and change from baseline in 6MWT through month 24 [24 months]

    Each subject will be compared to every other subject within a stratum over outcomes of all-cause mortality (death due to any cause), cumulative frequency of cardiovascular-related hospitalizations (number of times a subject is hospitalized for cardiovascular-related causes), change from baseline in NT-proBNP, and change from baseline in the total distance walked in 6 minutes (distance in meters). The hierarchical approach with the Finkelstein-Schoenfeld test will be applied and the test recognizes the greater importance of the mortality endpoint. Scores are transformed to -1, 0, +1. The alternative hypothesis is a subject in the TEER+OMT group will have a greater score than a subject in the placebo group.

Secondary Outcome Measures

  1. Evaluate effects of TEER on quality of life (QoL) through Month 24 [24 months]

    Change from Baseline to Month 24 as measured in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). The KCCQ is a 23-item questionnaire developed to measure health status and health-related quality of life in subjects with heart failure. Items include heart failure symptoms, impact on physical and social functions, and how their heart failure impacts their quality of life (QoL). An Overall Summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, scores are transformed to a range of 0-100 using the formula, 100*[(mean of questions actually answered) - 1]/4, in which higher scores reflect better health status. The Overall Summary score is the mean of the domains scores, range from 0 to 100, in which higher scores reflect better health status.

  2. Technical, device, and procedural success of TEER (in the TEER group only) [12 months]

    Technical, device, and procedural success of TEER as defined according to the definitions of the Mitral Valve Academic Research Consortium (MVARC)

Other Outcome Measures

  1. Effects of TEER on echocardiographic markers [24 months]

    Changes in forward stroke volume, ejection fraction, global longitudinal strain, etc.

  2. Effects of TEER on invasive haemodynamics (in the TEER group only) [1 day]

    Intraprocedural changes (pre- and post-TEER) in pulmonary pressures in the TEER-group

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion criteria (all must be present)

  • Proven ATTR-CM

  • Significant symptomatic MR (3+ or 4+ by independent echocardiographic core laboratory assessment)

  • Subject has been adequately treated per applicable standards, including for coronary artery disease and heart failure (e.g., diuretics)

  • New York Heart Association (NYHA) functional class II, III, or ambulatory IV

  • Local heart team has determined that mitral valve surgery will not be offered as a treatment option, even if the subject is randomized to the control group

  • Left ventricular ejection fraction ≥20%

  • Anatomical feasibility for TEER as per discretion of the implanting investigator

  • Age 18 years or older

  • Subject or guardian agrees to all provisions of the protocol, including the possibility of randomization to the Control group and returning for all required post-procedure follow-up visits, and has provided written informed consent

Exclusion criteria (all must be absent)

  • AL-associated cardiomyopathy

  • Aortic or tricuspid valve disease requiring surgery or transcatheter intervention

  • Severe right ventricular dysfunction

  • Hemodynamic instability requiring inotropic support or mechanical heart assistance

  • Leaflet anatomy which may preclude TEER, proper device positioning on the leaflets or sufficient reduction in mitral regurgitation by TEER

  • Life expectancy <12 months due to non-cardiac conditions

  • Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure

  • 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)

  • Active infections requiring current antibiotic therapy

  • Transesophageal echocardiography (TEE) is contraindicated or high risk

  • Pregnant or planning pregnancy within next 12 months

  • Currently participating in an investigational drug or another device study that has not reached its primary endpoint

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Medical University of Vienna

Investigators

  • Principal Investigator: Christian Nitsche, MD, PhD, Medical University of Vienna

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Christian Nitsche, Principle Investigator, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT06075823
Other Study ID Numbers:
  • 1830/2023
First Posted:
Oct 10, 2023
Last Update Posted:
Oct 10, 2023
Last Verified:
Oct 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:
Cardiomyopathies
Mitral Valve Insufficiency

Study Results

No Results Posted as of Oct 10, 2023