Transcatheter Edge-to-Edge Repair In Moderate and Exertional-Induced Severe MR (TIMER)

Sun Yat-sen University

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Mitral Regurgitation Functional

Treatments: Device: TEER; Drug: GDMT

Study type: Interventional

Funder types: Other

Identifiers

NCT07197021

TIMER

Details and patient eligibility

About

Transcatheter Edge-to-Edge Repair (TEER) has become an established alternative for the treatment of severe mitral regurgitation (MR). RESHAPE trial indicated that patients with moderate functional MR (FMR) and heart failure (HF) might benefit from TEER. However, it still not clear that TEER is effective for which subset of patients with FMR.

Hand-Gripping (HG), characterized with an increased venous return, preservation or increase of left ventricular (LV) afterload and systemic vascular resistance, has been identified as a means of stress test to identify exertion-induced mitral regurgitation. Most importantly, compared to exercise stress testing via treadmill running or cycling in patients with moderate FMR, HG demonstrates significantly higher feasibility and safety.

HG-induced severe MR reflects the reversibility of the regurgitation under stress, suggesting that reducing MR through TEER might alleviate LV volume overload, improve cardiac efficiency, and mitigate symptoms, which need to be validated in this trial.

TIMER is a multi-center, randomized, double blind, placebo-controlled trial. A total of 300 patients with moderate and exertional-induced severe MR will be randomized in a 1:1 ratio to the treatment with TEER and guideline-directed medical therapy (GDMT) or GDMT only.

The primary endpoint of this study is rehospitalization within 24 months.

Enrollment: 300 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Moderate functional mitral regurgitation
2. HG-induced severe functional mitral regurgitation
3. Left ventricular ejection fraction (LVEF) between 20% to 50%
4. Left ventricular end-systolic diameter (LVESD) ≤70 mm

Exclusion criteria

1. Stage D heart failure per ACC/AHA guidelines with hemodynamic instability or cardiogenic shock
2. Untreated symptomatic coronary artery disease requiring revascularization
3. Chronic obstructive pulmonary disease (COPD) requiring continuous oxygen therapy or long-term corticosteroids therapy
4. Severe pulmonary hypertension or moderate-to-severe right ventricular dysfunction
5. Aortic or tricuspid valve disease requiring surgical or transcatheter intervention
6. Life expectancy <12 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 2 patient groups, including a placebo group

TEER

Experimental group

Description:

TEER

Treatment:

Drug: GDMT

Device: TEER

Control group

Placebo Comparator group

Description:

GDMT

Treatment:

Drug: GDMT