- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05606718
Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling (DEFORM)
February 26, 2023 updated by: Xiao-dong Zhuang, Sun Yat-sen University
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).
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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
Study Type
Interventional
Enrollment (Anticipated)
98
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Xiaodong Zhuang, Dr
- Phone Number: +86 02087338190
- Email: zhuangxd3@mail.sysu.edu.cn
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510000
- Recruiting
- The Third Affiliated Hospital Of Sun Yat-sen University
-
Contact:
- Zhuoshan Huang, Dr
- Phone Number: 86 85252168
- Email: huangzhsh3@mail.sysu.edu.cn
-
Guangzhou, Guangdong, China, 510620
- Recruiting
- The First Affiliated Hospital of Sun Yat-sen University
-
Contact:
- Xiaodong Zhuang, Dr
- Phone Number: +86 02087338190
- Email: zhuangxd3@mail.sysu.edu.cn
-
Meizhou, Guangdong, China, 514799
- Recruiting
- The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital
-
Contact:
- Jinlai Liu, Prof
- Phone Number: 13503060663
- Email: liujinl@mail.sysu.edu.cn
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 90 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: dapagliflozin group
GDMT and dapagliflozin 10mg once daily
|
dapagliflozin 10mg once daily for 3 months after randomization
guideline-directed medical therapy (GDMT)
|
Active Comparator: control group
GDMT only
|
guideline-directed medical therapy (GDMT)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EROA of FMR
Time Frame: 3 months
|
Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
cardiac structure
Time Frame: 3 months
|
Change in RV measured by echocardiography from baseline to 12 weeks follow-up
|
3 months
|
MACE
Time Frame: 3 months
|
Occurrence of MACE in 12 weeks follow-up
|
3 months
|
cardiac function
Time Frame: 3 months
|
Change in serum NT-proBNP levels from baseline to 12 weeks follow-up
|
3 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Xiaodong Zhuang, Dr, First Affiliated Hospital, Sun Yat-Sen University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2022
Primary Completion (Anticipated)
June 30, 2023
Study Completion (Anticipated)
July 31, 2023
Study Registration Dates
First Submitted
October 30, 2022
First Submitted That Met QC Criteria
November 4, 2022
First Posted (Actual)
November 7, 2022
Study Record Updates
Last Update Posted (Estimate)
February 28, 2023
Last Update Submitted That Met QC Criteria
February 26, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DEFORM trial
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Functional Mitral Regurgitation
-
Abbott Medical DevicesCompletedFunctional Mitral Regurgitation | Degenerrative Mitral RegurgitationRussian Federation
-
Ancora Heart, Inc.CompletedMitral Regurgitation | Mitral Valve Regurgitation | Functional Mitral RegurgitationAustria, Lithuania, Germany
-
Heinrich-Heine University, DuesseldorfCompletedMitral Regurgitation | Functional Mitral Regurgitation | Degenerative Mitral Valve RegurgitationGermany
-
Cardiac Dimensions Pty LtdTerminatedAtrial Fibrillation | Functional Mitral Regurgitation | Atrial Functional Mitral RegurgitationAustralia, Greece
-
Mardil MedicalRecruitingFunctional Mitral RegurgitationCanada, Hungary, France, Germany, Netherlands, Panama, Poland
-
Shanghai Shenqi Medical Technology Co., LtdActive, not recruitingFunctional Mitral RegurgitationChina
-
Jenscare ScientificEnrolling by invitationFunctional Mitral RegurgitationChina
-
Asklepios proresearchAbbottWithdrawn
-
Mitre Medical Corp.BSWRI Cardiac Imaging Core Lab (CICL)Not yet recruitingIschemic Mitral Regurgitation | Functional Mitral RegurgitationUnited States
-
Barts & The London NHS TrustRecruitingAtrial Fibrillation | Functional Mitral Regurgitation | Functional Tricuspid RegurgitationUnited Kingdom
Clinical Trials on Dapagliflozin
-
AstraZenecaRecruitingHeart Failure and Impaired Kidney FunctionSpain, United States, France, Germany, Italy, Argentina, Czechia, Vietnam, Peru, China, Philippines, Saudi Arabia, Taiwan, Australia, Austria, Canada, Japan, Malaysia, Poland, Thailand, Israel, Brazil, Finland, Greece, United Kingdom, Mexico and more
-
Dong-A ST Co., Ltd.CompletedType2 DiabetesKorea, Republic of
-
AstraZenecaRecruitingLiver CirrhosisDenmark, Spain, Germany, United States, France, Australia, China, Netherlands, Belgium, Switzerland, Austria, United Kingdom, Taiwan, Canada, Czechia
-
AstraZenecaBristol-Myers SquibbCompletedType 2 Diabetes MellitusUnited Kingdom
-
AstraZenecaCompletedType 1 Diabetes MellitusJapan
-
Hiddo Lambers HeerspinkAstraZenecaCompletedChronic Kidney Diseases | ProteinuriaCanada, Malaysia, Netherlands
-
AstraZenecaCompletedType 1 Diabetes MellitusJapan
-
AstraZenecaCompletedChronic Kidney DiseaseUnited States
-
Daewoong Pharmaceutical Co. LTD.Active, not recruitingGlucose Metabolism Disorders | Diabetes Mellitus, Type 2 | Diabetes Mellitus | Endocrine System Diseases | Metabolic DiseaseChina
-
AstraZenecaRecruitingChronic Kidney DiseaseSpain, Italy, China, Vietnam, United States, Brazil, Canada, Malaysia, Poland, Taiwan, Austria, Japan, Turkey, Bulgaria, Chile, United Kingdom