About this trial
The goal of this clinical trial is to learn whether mitral valve transcatheter edge-to-edge repair (TEER) in addition to guideline-directed medical therapy (GDMT) can improve clinical outcomes and symptoms in heart failure patients with non-severe secondary mitral regurgitation (SMR) at rest and exercise-induced severe SMR.
The main questions it aims to answer are:
* Does mitral valve TEER in addition to GDMT lead to better overall clinical outcomes than GDMT alone in patients with heart failure and exercise-induced severe SMR? * Does mitral valve TEER reduce the risk of death, heart failure hospitalization, or worsening SMR during 12 months of follow-up compared with GDMT alone? * Does mitral valve TEER improve patients' quality of life compared with GDMT alone?
Participants will:
* Undergo screening assessments to confirm eligibility for the study. * Be randomly assigned to receive either GDMT alone or GDMT plus mitral valve TEER. * Attend follow-up visits at approximately 3 time points during a 12-month follow-up period. * Undergo clinical evaluations that are routinely performed in patients with heart failure and SMR, including assessment of symptoms, functional status, and cardiac function.
The patients' echocardiographic data will undergo an additional centralized assessment by an independent Core Laboratory.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Mild-to-moderate (1+/2+) SMR at rest
40 mm² EROA (30 mm² under low-flow condition) or
regurgitant volume ≥60 mL (45 mL under low-flow condition) or
regurgitant fraction ≥40% or
Disqualifiers
Hospitalization in past three months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina
LVEDD >70 mm
LVEF <20%
Evidence of transient ischemic attack or stroke within three months prior to intervention
Trial design
Parallel
Treatments tested in this trial
Guideline-Directed Medical Therapy (GDMT)
Other interventionParticipants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines. Medical treatment may include optimized pharmacological therapy such as beta-blockers, ACE inhibitors/ARBs/ARNI, mineralocorticoid receptor antagonists, diuretics, SGLT2-inhibitors and other indicated medications. Treatment is adjusted based on clinical status and treating physician judgment.
Mitral valve TEER
Procedure/SurgeryParticipants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines in combination with TEER of the mitral valve using the PASCAL Precision system (Edwards Lifesciences Sàrl). The procedure is performed via a minimally invasive transcatheter approach through femoral venous access to reduce SMR. Guideline-directed medical therapy is continued and optimized throughout follow-up according to standard of care.
Treatment groups
Trial outcomes
Primary outcomes
Four-step hierarchical composite primary endpoint; win ratio based on the following parameters: time to all-cause mortality at 12 months, time to first HF hospitalization, SMR progression (3+/4+) at rest, change in KCCQ score from baseline to 12 months.
The primary outcome is a single aggregated, unitless win ratio based on a four-step hierarchical composite primary endpoint at 12 months. Each patient in the GDMT+mitral valve TEER group will be compared with each patient in the GDMT group with respect to the following parameters in the following order: 1. time to all-cause mortality, days 2. time to first heart failure hospitalization, days 3. secondary mitral regurgitation progression (3+/4+) at rest and 4. change in KCCQ score from baseline to 12 months, where higher improvement or less deterioration wins; differences between patients less than 5 points are treated as ties (i.e. a between-patient threshold of 5 pts., KCCQ-values range from 0 to 100, higher values indicating better health). For each pairwise comparison, the first non-tied component determines a win for one group or a tie. The win ratio is the number of wins in the GDMT+ mitral valve TEER group divided by the number of wins in the GDMT group.
Secondary outcomes
Number of participants with cardiovascular death
Death due to cardiovascular causes during follow-up.
Number of participants with heart failure hospitalization
Hospitalization due to worsening heart failure requiring inpatient treatment.
Number of participants with myocardial infarction
Occurrence of myocardial infarction during follow-up.
Number of participants with stroke
Occurrence of ischemic or hemorrhagic stroke during follow-up.
Other outcomes
Number of participants with all-cause mortality
Death from any cause during the study follow-up period.
Number of participants with procedure-related complications during TEER
Complications occurring during or immediately after the TEER procedure.
Number of participants requiring non-elective cardiovascular surgery for device-related complications
Emergency or unplanned cardiovascular surgery related to the device or procedure.
Number of participants with endocarditis
Occurrence of infective endocarditis during follow-up.
Sponsors and contacts
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