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

NCT05848102 | Unknown Phase 4 DMC

• 1 other identifier: DEFORM Study
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 3

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.

Conditions

Functional Mitral Regurgitation

Keywords

dapagliflozin; Guideline directed medical therapy

Outcome Measures

Primary Outcomes (1)

• Mitral valve effective regurgitant orifice area change

  Evaluated by echocardiography at baseline and 6 month

  From baseline to 6 month

Secondary Outcomes (5)

• myocardial fibrosis change

  from baseline to 6 month

• NT-proBNP change

  from baseline to 6 month

• KCCQ-12 score

  from baseline to 6 month

• cardiopulmonary exercise testing score

  from baseline to 6 month

• Distance of 6 minutes walking test

  from baseline to 6 month

Study Arms (2)

Dapagliflozin arm

EXPERIMENTAL

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.

Drug: dapagliflozin

GDMT arm

NO INTERVENTION

In the guideline directed medical therapy (GDMT) arm, participants with functional mitral regurgitation of more than moderate and left ventricular ejection fraction of more than 40% will continue to maintain the original treatment of GDMT for 6 month.

Interventions

dapagliflozin DRUG

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

Dapagliflozin arm

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agree to get enrolled;
• Age 18-90 years old, gender is not limited;
• More than moderated FMR ( EROA by echocardiography ≥0.2cm2) , and LVEF more than 40%;
• The structure of mitral valve leaflets and chordae is normal;
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Sun Yat-sen University: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator
• Jieyang People's Hospital: collaborator
• Eighth Affiliated Hospital, Sun Yat-sen University: collaborator
• Affiliated Hospital of Guangdong Medical University: collaborator
• Yuebei People's Hospital: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator

Study Sites (3)

The Third Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

The First Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510620, China

RECRUITING

The Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, 510260, China

RECRUITING

MeSH Terms

Interventions

dapagliflozin

Study Officials

• Xiaodong Zhuang, PhD

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaodong Zhuang, PhD

CONTACT

(+86)13760755035; zhuangxd3@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 13, 2023
• First Posted: May 8, 2023
• Study Start: December 23, 2022
• Primary Completion: October 23, 2024
• Study Completion: April 23, 2025
• Last Updated: May 8, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)