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

Functional Mitral Regurgitation Clinical Trial

— DEFORM  

Official title:

Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Fibrosis (DEFORM): a Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05848102
• Other study ID #: DEFORM Study
• Status: Recruiting
• Phase: Phase 4
• Start date: December 23, 2022
• Est. completion date: April 23, 2025

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: Xiaodong Zhuang, PhD
• Phone: (+86)13760755035
• Email: zhuangxd3[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 166
• Est. completion date: April 23, 2025
• Est. primary completion date: October 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 ß 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.

Related Conditions & MeSH terms

• Functional Mitral Regurgitation
• Mitral Valve Insufficiency

Intervention

Drug:
• dapagliflozin
FORXIGA(Dapagliflozin Tablets), manufacturer/marketer: AstraZeneca, salt composition: Dapagliflozin (10mg), one tablet once and once a day.

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 Second Affiliated Hospital of Guangzhou Medical University	Guanzhou	Guangdong

Sponsors (9)

Lead Sponsor	Collaborator
Sun Yat-sen University	Affiliated Hospital of Guangdong Medical University, Eighth Affiliated Hospital, Sun Yat-sen University, First Affiliated Hospital, Sun Yat-Sen University, Jieyang People's Hospital, Second Affiliated Hospital of Guangzhou Medical University, Third Affiliated Hospital, Sun Yat-Sen University, Yuebei People's Hospital, Zhongshan People's Hospital, Guangdong, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitral valve effective regurgitant orifice area change	Evaluated by echocardiography at baseline and 6 month	From baseline to 6 month
Secondary	myocardial fibrosis change	Evaluated by cardiac magnetic resonance	from baseline to 6 month
Secondary	NT-proBNP change	N-terminal pro-brain natriuretic peptide(NT-proBNP) tested in Venous blood sample	from baseline to 6 month
Secondary	KCCQ-12 score	Cardiomyopathy questionnaire (Kansas City):(KCCQ-12)	from baseline to 6 month
Secondary	cardiopulmonary exercise testing score	Cardiorespiratory functional assessment	from baseline to 6 month
Secondary	Distance of 6 minutes walking test		from baseline to 6 month