Edge-to-edge Mitral Valve Repair in ATTR-CM (MILLENNIAL)

December 8, 2023 updated by: Christian Nitsche, Medical University of Vienna

Effectiveness and Safety of Edge-to-edge MItral vaLve Repair in Patients With Severe mitraL rEgurgitatioN aNd cardIac ATTR amyLoidosis

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 another investigational device study that has not reached its primary endpoint

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate effects of TEER on quality of life (QoL) through Month 24
Time Frame: 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.
24 months
Technical, device, and procedural success of TEER (in the TEER group only)
Time Frame: 12 months
Technical, device, and procedural success of TEER as defined according to the definitions of the Mitral Valve Academic Research Consortium (MVARC)
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of TEER on echocardiographic markers
Time Frame: 24 months
Changes in forward stroke volume, ejection fraction, global longitudinal strain, etc.
24 months
Effects of TEER on invasive haemodynamics (in the TEER group only)
Time Frame: 1 day
Intraprocedural changes (pre- and post-TEER) in pulmonary pressures in the TEER-group
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2024

Primary Completion (Estimated)

December 12, 2027

Study Completion (Estimated)

December 12, 2028

Study Registration Dates

First Submitted

September 27, 2023

First Submitted That Met QC Criteria

October 4, 2023

First Posted (Actual)

October 10, 2023

Study Record Updates

Last Update Posted (Estimated)

December 11, 2023

Last Update Submitted That Met QC Criteria

December 8, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1830/2023

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Mitral Regurgitation

Clinical Trials on TEER

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe