About this trial

Functional mitral regurgitation is a highly dynamic disease. Some patients exhibit only moderate(2+) functional mitral regurgitation at rest, which deteriorates to moderate-to-severe or severe FMR(3+ or 4+) during stress-termed dynamic severe functional mitral regurgitation. Observational studies link this condition to worse outcomes, with mitral valve intervention offering potential benefits; however, high-quality evidence remains lacking.

The Transcatheter Edge-to-Edge Repair In DynaMic sEvere Functional Mitral Regurgitation trial aims to assess the safety and effectiveness of transcatheter edge-to-edge repair plus guideline-directed medical therapy versus guideline-directed medical therapy alone in symptomatic chronic heart failure patients with dynamic severe functional mitral regurgitation, defined as moderate regurgitation at rest deteriorating to severe during handgrip stress echocardiography.

This prospective, multi-center, randomized trial enrolls patients with dynamic severe functional mitral regurgitation confirmed by a core laboratory using handgrip stress echocardiography. Patients are randomized 1:1 to transcatheter edge-to-edge repair plus medical therapy or medical therapy alone. The primary endpoint is the composite of Cardiovascular death or heart failure hospitalization over the entire period.

This trial will provide critical evidence on transcatheter edge-to-edge repair in patients with dynamic severe functional mitral regurgitation, informing future treatment recommendations.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Clinically significant functional mitral regurgitation (MR (2+) at rest that deteriorates to moderate-to-severe (3+) or severe (4+) FMR during standardized handgrip stress echocardiography, with ΔEROA ≥0.1cm²) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate

Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization.

Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 days preceding randomization

Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate

Disqualifiers

Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).

Status 1 heart transplant or prior orthotropic heart transplantation.

Introduction of a new heart failure drug class within the last 2 weeks prior to randomization.

Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.

Trial design

Design model

Parallel

Treatments tested in this trial

TEER
Device
TEER
GDMT
Drug
GDMT

Treatment groups

540 Participants

are divided into 2 treatment groups

Group A: TEER+GDMTExperimental treatment 2 interventions

Group B: Control groupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

The rate of the recurrent composite of cardiovascular (CV) death and heart failure hospitalization (HFH) over the entire follow-up period (analyzed when the last subject completes 12 m of follow up).

Cardiovascular death or heart failure hospitalization (HFH) occurring within 2 years after enrollment

Time frame

2 years

Secondary outcomes

1

Mitral Regurgitation (MR severity reduction to MR ≤2+ under stress) at 12 months

Mitral Regurgitation (MR severity reduction to MR \<=2+) at 1 year, 2 years and 5 years

Time frame

5 years

2

Changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months.

KCCQ within 2 years and 5 years after enrollment

Time frame

5 years

3

Changes in 6-minute walk test (6MWT) distance at 12 months.

6MWT within 2 years and 5 years after enrollment

Time frame

5 years

4

Changes in NYHA functional class at 12 months.

NYHA

Time frame

5 years

Other outcomes

1

Composite of all-cause mortality, stroke, myocardial infarction, new need for renal replacement therapy and non-elective cardiovascular surgery for device related complications in the Device group at 30 days

Time frame

30 days

TEER In dynaMic sEvere Functional Mitral Regurgitation (TIMER)

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts