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

Mitral Regurgitation Clinical Trial

— MILLENNIAL  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06075823
• Other study ID #: 1830/2023
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: December 12, 2028

Study information

• Verified date: December 2023
• Source: Medical University of Vienna
• Contact: Christian Nitsche, MD, PhD
• Phone: 0043 1 40400 46142
• Email: christian.nitsche[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 12, 2028
• Est. primary completion date: December 12, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Mitral Regurgitation
• Mitral Valve Insufficiency

Intervention

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

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

References & Publications (4)

Chacko L, Karia N, Venneri L, Bandera F, Passo BD, Buonamici L, Lazari J, Ioannou A, Porcari A, Patel R, Razvi Y, Brown J, Knight D, Martinez-Naharro A, Whelan C, Quarta CC, Manisty C, Moon J, Rowczenio D, Gilbertson JA, Lachmann H, Wechelakar A, Petrie A — View Citation

Dona C, Nitsche C, Koschutnik M, Heitzinger G, Mascherbauer K, Kammerlander AA, Dannenberg V, Halavina K, Rettl R, Duca F, Traub-Weidinger T, Puchinger J, Gunacker PC, Lamm G, Vock P, Lileg B, Philipp V, Staudenherz A, Calabretta R, Hacker M, Agis H, Bart — View Citation

Nitsche C. Echocardiographic tracking of transthyretin cardiomyopathy: which parameters matter the most? Eur J Heart Fail. 2022 Sep;24(9):1713-1715. doi: 10.1002/ejhf.2639. Epub 2022 Aug 12. No abstract available. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects of TEER on echocardiographic markers	Changes in forward stroke volume, ejection fraction, global longitudinal strain, etc.	24 months
Other	Effects of TEER on invasive haemodynamics (in the TEER group only)	Intraprocedural changes (pre- and post-TEER) in pulmonary pressures in the TEER-group	1 day
Primary	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	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	Evaluate effects of TEER on quality of life (QoL) through Month 24	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
Secondary	Technical, device, and procedural success of TEER (in the TEER group only)	Technical, device, and procedural success of TEER as defined according to the definitions of the Mitral Valve Academic Research Consortium (MVARC)	12 months