Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling

Functional Mitral Regurgitation Clinical Trial

— DEFORM  

Official title:

Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05606718
• Other study ID #: DEFORM trial
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: February 2023
• Source: Sun Yat-sen University
• Contact: Xiaodong Zhuang, Dr
• Phone: +86 02087338190
• Email: zhuangxd3[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: July 31, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Functional Mitral Regurgitation
• Mitral Valve Insufficiency

Intervention

Drug:
• Dapagliflozin
dapagliflozin 10mg once daily for 3 months after randomization

Other:
• guideline-directed medical therapy (GDMT)
guideline-directed medical therapy (GDMT)

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital	Meizhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EROA of FMR	Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up	3 months
Secondary	cardiac structure	Change in RV measured by echocardiography from baseline to 12 weeks follow-up	3 months
Secondary	MACE	Occurrence of MACE in 12 weeks follow-up	3 months
Secondary	cardiac function	Change in serum NT-proBNP levels from baseline to 12 weeks follow-up	3 months