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

Official title

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

Overview

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.

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.

Interventions

• Device TEER
  transcatheter edge-to-edge mitral valve repair for significant mitral regurgitation
• Other Optimal Medical Therapy
  optimal heart failure management of ATTR-CM

Primary outcome measures

• 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]

Secondary outcome measures (2)

• Evaluate effects of TEER on quality of life (QoL) through Month 24 [Time frame: 24 months]
• Technical, device, and procedural success of TEER (in the TEER group only) [Time frame: 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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
• 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 PMID 36008266
• 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 a PMID 35779241
• 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

Identifiers

NCT: NCT06075823 · 1830/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗