Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling

NCT ID: NCT05606718

Last Updated: 2023-02-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2023-07-31

Brief Summary

Functional mitral regurgitation (FMR) leads to various adverse outcomes. Cardiac remodeling (CR) and myocardial fibrosis (MF) are closely related to FMR, forming a vicious circle of CR-FMR-MF and resulting in the end-stage heart failure (HF). The optimal therapeutic strategies of FMR require to effectively break the vicious circle of CR-FMR-MF and still remain full of controversy, especially in the appropriate selection of patients suitable for transcatheter treatment. Regardless, adequate guideline-directed medical therapy (GDMT) is always the most important therapy of FMR. Currently GDMT for FMR included β-blockers, renin-angiotensin system (RAS) inhibitors and mineralocorticoid receptor antagonists (MRA). Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, have been proven to be effectively in reducing cardiovascular death and worsening HF in HF patients. However, there is still no evidence support the use of SGLT2i in FMR therapy due to the lack of relevant clinical trial. The DEFORM trial aims to assess the efficacy of dapagliflozin in reducing the extent of mitral regurgitation and myocardial fibrosis in FMR patients. DEFORM trial is a multi-center, prospective, randomized, parallel controlled, investigator-initiated trial enrolling a planned 98 FMR patients. Patients will be randomly assigned in a 1:1 ratio to either dapagliflozin 10mg once daily for 3 months or placebo. The primary outcome is the change in effective regurgitant orifice area (EROA) of mitral regurgitation measured by echocardiography. Secondary end-points include change change in regurgitant volume (RV), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) (echocardiography), change in NT-proBNP levels and occurrence of major adverse cardiac events (MACEs).

Detailed Description

Inclusion criteria:

• Patients aged >18 years and <90 years
• LVEF<60% and EROA of mitral regurgitation≥0.2cm2 on echocardiography
• The structure of mitral valve leaf and chordae tendineae is normal
• Patients have received GDMT for FMR including a stable, optimized dose of β-blocker and RAAS inhibitors for at least 2 weeks
• No intravenous anti-heart failure drugs used for the past 2 weeks
• Written informed consent

Exclusion criteria:

• Allergic to dapagliflozin, or angioedema
• Already taking dapagliflozin or other SGLT2 inhibitors
• Presence of primary structural damage to the mitral valve, such as rheumatic heart disease, mitral valve prolapses
• Non-dialysis chronic kidney disease (CKD) patients with eGFR <30ml/min/1.73m2 or dialysis patients
• Acute myocardial infarction and acute myocarditis occurred within 3 months
• Revascularization procedure, CRT, TMVR, surgical valve repair or replacement were performed or planed 3 months before or after enrollment
• Combining significant aortic valve diseases (moderate or severe regurgitation or stenosis)
• Combining hyperthyroidism while thyroid function has not returned to normal
• Pregnant or lactation women

Conditions

Functional Mitral Regurgitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dapagliflozin group

GDMT and dapagliflozin 10mg once daily

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

dapagliflozin 10mg once daily for 3 months after randomization

guideline-directed medical therapy (GDMT)

Intervention Type: OTHER

guideline-directed medical therapy (GDMT)

control group

GDMT only

Group Type: ACTIVE_COMPARATOR

guideline-directed medical therapy (GDMT)

Intervention Type: OTHER

guideline-directed medical therapy (GDMT)

Interventions

Dapagliflozin

dapagliflozin 10mg once daily for 3 months after randomization

Intervention Type: DRUG

guideline-directed medical therapy (GDMT)

guideline-directed medical therapy (GDMT)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients aged >18 years and <90 years
• LVEF<60% and EROA of mitral regurgitation≥0.2cm2 on echocardiography
• The structure of mitral valve leaf and chordae tendineae is normal
• Patients have received GDMT for FMR including a stable, optimized dose of β-blocker and RAAS inhibitors for at least 2 weeks

Exclusion Criteria

• Allergic to dapagliflozin, or angioedema
• Already taking dapagliflozin or other SGLT2 inhibitors
• Presence of primary structural damage to the mitral valve, such as rheumatic heart disease, mitral valve prolapses
• Non-dialysis chronic kidney disease (CKD) patients with eGFR <30ml/min/1.73m2 or dialysis patients
• Acute myocardial infarction and acute myocarditis occurred within 3 months
• Revascularization procedure, CRT, TMVR, surgical valve repair or replacement were performed or planed 3 months before or after enrollment
• Combining significant aortic valve diseases (moderate or severe regurgitation or stenosis)
• Combining hyperthyroidism while thyroid function has not returned to normal
• Pregnant or lactation women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Xiao-dong Zhuang

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaodong Zhuang, Dr

Role: STUDY_CHAIR

First Affiliated Hospital, Sun Yat-Sen University

Locations

The Third Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

The First Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital

Meizhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaodong Zhuang, Dr

Role: CONTACT

zhuangxd3@mail.sysu.edu.cn

+86 02087338190

Facility Contacts

Zhuoshan Huang, Dr

Role: primary

huangzhsh3@mail.sysu.edu.cn

86 85252168

Xiaodong Zhuang, Dr

Role: primary

zhuangxd3@mail.sysu.edu.cn

+86 02087338190

Jinlai Liu, Prof

Role: primary

liujinl@mail.sysu.edu.cn

13503060663

Other Identifiers

DEFORM trial

Identifier Type: -

Identifier Source: org_study_id