Edge-to-edge mitral valve repair for ATTR-CM with mitral regurgitation
Official title: Effectiveness and Safety of Edge-to-edge MItral vaLve Repair in Patients With Significant mitraL rEgurgitatioN aNd cardIac ATTR amyLoidosis
Run by Medical University of Vienna · NCT06075823 · Data updated 2026-11-12
This trial tests whether adding transcatheter edge-to-edge mitral valve repair helps patients with ATTR-associated cardiomyopathy and significant mitral regurgitation compared with standard medical therapy alone.
Quick facts
| Study type | Interventional |
|---|---|
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 106 (estimated) |
| Sponsor | Medical University of Vienna Academic / other |
| Locations | 10 sites (Graz and 9 other locations) |
| Status | Recruiting |
| Started | January 1, 2024 |
| Main results expected | December 12, 2027 |
| Study ends | December 12, 2028 |
| Registry record updated | October 16, 2026 |
| Trial ID | NCT06075823 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults (18+) with proven ATTR-CM, symptomatic moderate-to-severe or severe MR, NYHA II–IV, suitable anatomy for TEER, and deemed unsuitable for surgical repair.
✕Probably not a fit
Patients without sufficient anatomical suitability for TEER, those with non-cardiac factors limiting benefit, or those who do not tolerate or require TEER may not experience improvements.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
MILLENNIAL is a multicenter, prospective, randomized trial comparing TEER plus optimal medical therapy to optimal medical therapy alone in adults with proven ATTR-CM and moderate-to-severe or severe symptomatic mitral regurgitation. Eligible participants have non-surgical candidacy for mitral valve repair, adequate anatomy for TEER, and are on standard heart failure treatment. The primary endpoint is a hierarchical composite at 12 months including mortality, unplanned cardiovascular hospitalizations, and functional/quality-of-life measures analyzed with a win ratio, with NT-proBNP as a key secondary endpoint. The study allows ATTR-specific therapy at the physician's discretion and does not permit cross-over within the first year. Safety endpoints include device and procedural success; exploratory endpoints cover intraprocedural haemodynamics and other assessments. The trial aims to determine if TEER can improve functional capacity, quality of life, and clinical outcomes beyond conservative management.
Why it matters
Potential benefit: If successful, TEER could improve symptoms, exercise capacity, and overall outcomes for ATTR-CM patients with significant mitral regurgitation.
How similar studies have gone: Prior TEER trials in broader mitral regurgitation populations support safety and potential benefit, but this ATTR-CM–specific population is novel and exploratory.
Who can join: the full rules
Show full inclusion / exclusion 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 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
Where it's running
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Medical University of Graz, Division of Cardiology
Graz, Austria Recruiting -
Ordensklinikum Linz Elisabethinen, Internal Medicine 2, Cardiology
Linz, Austria Recruiting -
University Hospital St. Pölten, Department of Internal Medicine 3
Sankt Pölten, Austria Recruiting -
Clinic Favoriten, 5th Medical Department, Cardiology
Vienna, Austria Recruiting -
Medical University of Vienna
Vienna, Austria Recruiting -
University Hospital Heidelberg, Department of Cardiology, Angiology and Respiratory Medicine
Heidelberg, Germany Recruiting
Show 4 more locations
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LMU University Hospital, Department of Medicine I
München, Germany Recruiting -
ASST Spedali Civili di Brescia, Cardiology
Brescia, Italy Recruiting -
Hannover Medical School, Department of Cardiology and Angiology
Hanover, Germany Not yet recruiting -
ASST Papa Giovanni XXIII, Cardiovascular Department
Bergamo, Italy Not yet recruiting
Study contacts
- Principal investigator: Christian Nitsche, MD, PhD — Medical University of Vienna
- Study coordinator: Christian Nitsche, MD, PhD
- Email: christian.nitsche@meduniwien.ac.at
- Phone: 0043 1 40400 46142
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Posterior Mitral Leaflet Replacement to Reduce Mitral Regurgitation
This early feasibility trial tests the MR-ace Implant and Delivery System to see if it can reduce symptoms and leaks in people with moderate-to-severe functional mitral regurgitation.
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Replacing the native mitral valve with the ReValve System
This study will test whether replacing the native mitral valve with the ReValve System helps adults with symptomatic, clinically significant mitral regurgitation who are appropriate candidates for mitral valve surgery.
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Mitral valve replacement with the SATURN TMVR system for severe mitral regurgitation
This study tests whether the SATURN TS transcatheter mitral valve replacement can be safely implanted and work well in adults with severe mitral regurgitation who are high-risk for open-heart surgery.
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Outcomes after new edge-to-edge mitral valve repair
This project will follow people with mitral regurgitation who receive transcatheter edge-to-edge repair at Amsterdam UMC to see how they do long-term and whether patient selection can be improved.
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Surgical implantation of a polymer prosthetic mitral or aortic valve
This will test a surgically implanted polymer heart valve to see if it is safe and works well for adults who need mitral or aortic valve replacement.
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GeminiOne transcatheter edge-to-edge repair for severe symptomatic mitral regurgitation
This trial will try the GeminiOne TEER system to treat adults with severe, symptomatic mitral regurgitation who are high surgical risk or have not improved with medical therapy.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.