Clinical trial NCT05848102: Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Fibrosis (DEFORM)
Official title: Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Fibrosis (DEFORM): a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Functional Mitral Regurgitation
Keywords: dapagliflozin
Guideline directed medical therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Second Affiliated Hospital of Guangzhou Medical University
name: Jieyang People's Hospital
name: Eighth Affiliated Hospital, Sun Yat-sen University
name: Affiliated Hospital of Guangdong Medical University
name: Yuebei People's Hospital
name: Zhongshan People's Hospital, Guangdong, China
First posted: 2023-05-08
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mitral valve effective regurgitant orifice area change
timeFrame: From baseline to 6 month
Secondary outcomes:
measure: myocardial fibrosis change
timeFrame: from baseline to 6 month
measure: NT-proBNP change
timeFrame: from baseline to 6 month
measure: KCCQ-12 score
timeFrame: from baseline to 6 month
measure: cardiopulmonary exercise testing score
timeFrame: from baseline to 6 month
measure: Distance of 6 minutes walking test
timeFrame: from baseline to 6 month
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guanzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Xiaodong Zhuang, PhD
role: PRINCIPAL_INVESTIGATOR
References: