Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Fibrosis (DEFORM)

Phase 4

Recruiting

• Conditions: Functional Mitral Regurgitation
• Interventions: Drug: dapagliflozin

• Registration Number: NCT05848102
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The goal of this clinical trial is to learn about the effect of dapagliflozin on reducing the degree of mitral regurgitation and myocardial fibrosis in patients with functional mitral regurgitation (FMR) of more than moderate and left ventricular ejection fraction (LVEF) more than 40%.

The main question\[s\] it aims to answer are:

* For FMR patients with EF\>40%, whether adding SGLT2 to guideline directed medical therapy (GDMT) can reduce MR degree and myocardial fibrosis, as well as improve patient's cardio-pulmonary function and quality of life is unknown.

* For FMR patients with EF\>40%, whether adding SGLT2 to GDMT can decelerate the progression of FMR to end-stage heart failure, reduce the demand for percutaneous mitral valve repair and improve the prognosis is unknown.

Participants in dapagliflozin arm will add dapagliflozin of 10 mg/d orally for 6 months on the basis of regular GDMT for FMR. Researchers will compare the dapagliflozin arm to the GDMT arm who only accept the regular GDMT to see if the effective regurgitant orifice area was decreased.

The primary endpoint was the effective regurgitant orifice area(EROA) change from baseline to 6 months.

The secondary endpoints include the cardiac magnetic resonance assessment of myocardial fibrosis, the N-terminal fragment of the pro brain natriuretic peptides(NT-pro BNP), maximal exercise capacity by cardiopulmonary exercise testing, distance in the 6 minutes walking test, Kansas City cardiomyopathy questionnaire and Cardiovascular events.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-23
• Status Verified: 2023-04
• Study First Submitted: 2023-04-13
• Study First Submitted QC: 2023-04-27
• Last Update Submitted: 2023-04-27
• Study First Posted: 2023-05-08
• Last Update Posted: 2023-05-08
• Primary Completion: 2024-10-23
• Study Completion: 2025-04-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 166

Inclusion Criteria

1. Agree to get enrolled;
2. Age 18-90 years old, gender is not limited;
3. More than moderated FMR ( EROA by echocardiography ≥0.2cm2) , and LVEF more than 40%;
4. The structure of mitral valve leaflets and chordae is normal;
5. GDMT for FMR has been taken orally for more than 2 weeks, and the dose has not been adjusted for more than 2 weeks (If there is no contraindication, the drugs includes β blockers, the renin-angiotensin system inhibitors [Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers/angiotensin receptor neprilysin inhibitor], aldosterone receptor antagonists), and for the last 2 weeks no intravenous drug for heart failure were used.

Exclusion Criteria

1. Have indication for dapagliflozin;
2. Angioedema, or allergic to dapagliflozin;
3. Already taking Dapagliflozin or other SGLT2 inhibitors;
4. Primary mitral valve structural damage, such as rheumatic heart disease, mitral valve prolapse;
5. Non-dialysis patients with estimated glomerular filtration rate<30ml/min/1.73m2;
6. Dialysis patients;
7. Acute myocardial infarction, acute myocarditis, or percutaneous transluminal coronary intervention, coronary artery bypass grafting and other vascular reconstruction operations have occurred within 3 months;
8. Those who plan to take vascular reconstruction, cardiac resynchronization therapy, percutaneous mitral valve repair, surgical valve repair or replacement within 3 months after enrollment;
9. Complications of obvious aortic valve disease (more than moderate stenosis or more than moderate regurgitation);
10. Thyroid function combined with hyperthyroidism has not returned to normal;
11. Pregnant and lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin arm	dapagliflozin	In the Dapagliflozin arm, participants with functional mitral regurgitation of more than moderate and left ventricular ejection fraction of more than 40% will add oral drug of Forxiga (Dapagliflozin, specification: 10mg) of 10 mg per day on the basis of regular guideline directed medical therapy for functional mitral regurgitation for 6 months.

Primary Outcome Measures

Name	Time	Method
Mitral valve effective regurgitant orifice area change	From baseline to 6 month	Evaluated by echocardiography at baseline and 6 month

Secondary Outcome Measures

Name	Time	Method
myocardial fibrosis change	from baseline to 6 month	Evaluated by cardiac magnetic resonance
NT-proBNP change	from baseline to 6 month	N-terminal pro-brain natriuretic peptide(NT-proBNP) tested in Venous blood sample
cardiopulmonary exercise testing score	from baseline to 6 month	Cardiorespiratory functional assessment
KCCQ-12 score	from baseline to 6 month	Cardiomyopathy questionnaire (Kansas City):(KCCQ-12)
Distance of 6 minutes walking test	from baseline to 6 month

Trial Locations

Locations (3)

The First Affiliated Hospital of Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China

The Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guanzhou, Guangdong, China

The Third Affiliated Hospital of Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China