Clinical trial NCT06075823: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Mitral Regurgitation
ATTR-Cardiomyopathy
Edge-to-Edge Mitral Valve Repair
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2023-10-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: 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
timeFrame: 24 months
Secondary outcomes:
measure: Evaluate effects of TEER on quality of life (QoL) through Month 24
timeFrame: 24 months
measure: Technical, device, and procedural success of TEER (in the TEER group only)
timeFrame: 12 months
Other outcomes:
measure: Effects of TEER on echocardiographic markers
timeFrame: 24 months
measure: Effects of TEER on invasive haemodynamics (in the TEER group only)
timeFrame: 1 day
Locations:
Study officials:
affiliation: Medical University of Vienna
name: Christian Nitsche, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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, 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.
citation: 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.
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.