Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling

NCT05606718 | Unknown Phase 4 DMC

• 1 other identifier: DEFORM trial
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Functional Mitral Regurgitation

Outcome Measures

Primary Outcomes (1)

• EROA of FMR

  Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up

  3 months

Secondary Outcomes (3)

• cardiac structure

  3 months

• MACE

  3 months

• cardiac function

  3 months

Study Arms (2)

dapagliflozin group

EXPERIMENTAL

GDMT and dapagliflozin 10mg once daily

Drug: Dapagliflozin; Other: guideline-directed medical therapy (GDMT)

control group

ACTIVE COMPARATOR

GDMT only

Other: guideline-directed medical therapy (GDMT)

Interventions

Dapagliflozin DRUG

dapagliflozin 10mg once daily for 3 months after randomization

dapagliflozin group

guideline-directed medical therapy (GDMT) OTHER

guideline-directed medical therapy (GDMT)

control group; dapagliflozin group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

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 Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital

Meizhou, Guangdong, 514799, China

RECRUITING

MeSH Terms

Interventions

dapagliflozin

Study Officials

• Xiaodong Zhuang, Dr

  First Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Central Study Contacts

Xiaodong Zhuang, Dr

CONTACT

+86 02087338190; zhuangxd3@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: October 30, 2022
• First Posted: November 7, 2022
• Study Start: April 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2023
• Last Updated: February 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)