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

NCT06075823 | Not Yet Recruiting

• 1 other identifier: 1830/2023
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Mitral Regurgitation; ATTR-Cardiomyopathy; Edge-to-Edge Mitral Valve Repair

Outcome Measures

Primary Outcomes (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

  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 Outcomes (2)

• Evaluate effects of TEER on quality of life (QoL) through Month 24

  24 months

• Technical, device, and procedural success of TEER (in the TEER group only)

  12 months

Other Outcomes (2)

• Effects of TEER on echocardiographic markers

  24 months

• Effects of TEER on invasive haemodynamics (in the TEER group only)

  1 day

Study Arms (2)

Interventional

EXPERIMENTAL

TEER + Optimal Medical Therapy

Device: TEER; Other: Optimal Medical Therapy

Control

ACTIVE COMPARATOR

Optimal Medical Therapy alone

Other: Optimal Medical Therapy

Interventions

TEER DEVICE

transcatheter edge-to-edge mitral valve repair for significant mitral regurgitation

Interventional

Optimal Medical Therapy OTHER

optimal heart failure management of ATTR-CM

Control; Interventional

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Related Publications (4)

• 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.

  PMID: 30280640 BACKGROUND

• 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, Bartko P, Hengstenberg C, Fontana M, Goliasch G, Mascherbauer J. Unveiling Cardiac Amyloidosis, its Characteristics, and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair. JACC Cardiovasc Interv. 2022 Sep 12;15(17):1748-1758. doi: 10.1016/j.jcin.2022.06.009. Epub 2022 Aug 22.

  PMID: 36008266 RESULT

• 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, Moody WE, Steeds RP, Potena L, Riefolo M, Leone O, Rapezzi C, Hawkins PN, Gillmore JD, Fontana M. Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis. Eur J Heart Fail. 2022 Sep;24(9):1700-1712. doi: 10.1002/ejhf.2606. Epub 2022 Jul 27.

  PMID: 35779241 RESULT

• 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.

  PMID: 35906799 RESULT

MeSH Terms

Conditions

Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Christian Nitsche, MD, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian Nitsche, MD, PhD

CONTACT

0043 1 40400 46142; christian.nitsche@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 10, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2028
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share