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

Primary Purpose

Functional Mitral Regurgitation

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Dapagliflozin
guideline-directed medical therapy (GDMT)
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Functional Mitral Regurgitation

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • The Third Affiliated Hospital of Sun Yat-Sen UniversityRecruiting
  • The First Affiliated Hospital of Sun Yat-Sen UniversityRecruiting
  • The Third Affiliated Hospital of Sun Yat-sen University Yuedong HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

dapagliflozin group

control group

Arm Description

GDMT and dapagliflozin 10mg once daily

GDMT only

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

cardiac structure
Change in RV measured by echocardiography from baseline to 12 weeks follow-up
MACE
Occurrence of MACE in 12 weeks follow-up
cardiac function
Change in serum NT-proBNP levels from baseline to 12 weeks follow-up

Full Information

First Posted
October 30, 2022
Last Updated
February 26, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05606718
Brief Title
Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling
Acronym
DEFORM
Official Title
Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2022 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
Inclusion criteria: 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 No intravenous anti-heart failure drugs used for the past 2 weeks Written informed consent Exclusion criteria: 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Mitral Regurgitation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
98 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
dapagliflozin group
Arm Type
Experimental
Arm Description
GDMT and dapagliflozin 10mg once daily
Arm Title
control group
Arm Type
Active Comparator
Arm Description
GDMT only
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
dapagliflozin 10mg once daily for 3 months after randomization
Intervention Type
Other
Intervention Name(s)
guideline-directed medical therapy (GDMT)
Intervention Description
guideline-directed medical therapy (GDMT)
Primary Outcome Measure Information:
Title
EROA of FMR
Description
Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up
Time Frame
3 months
Secondary Outcome Measure Information:
Title
cardiac structure
Description
Change in RV measured by echocardiography from baseline to 12 weeks follow-up
Time Frame
3 months
Title
MACE
Description
Occurrence of MACE in 12 weeks follow-up
Time Frame
3 months
Title
cardiac function
Description
Change in serum NT-proBNP levels from baseline to 12 weeks follow-up
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodong Zhuang, Dr
Phone
+86 02087338190
Email
zhuangxd3@mail.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhuang, Dr
Organizational Affiliation
First Affiliated Hospital, Sun Yat-Sen University
Official's Role
Study Chair
Facility Information:
Facility Name
The Third Affiliated Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhuoshan Huang, Dr
Phone
86 85252168
Email
huangzhsh3@mail.sysu.edu.cn
Facility Name
The First Affiliated Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510620
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhuang, Dr
Phone
+86 02087338190
Email
zhuangxd3@mail.sysu.edu.cn
Facility Name
The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital
City
Meizhou
State/Province
Guangdong
ZIP/Postal Code
514799
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinlai Liu, Prof
Phone
13503060663
Email
liujinl@mail.sysu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling

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