Functional Mitral RegurgitationPhase 4DEFORMNCT05606718
Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling
A Phase 4 study testing Dapagliflozin and guideline-directed medical therapy (GDMT) in people with Functional Mitral Regurgitation, run by Sun Yat-sen University at 3 sites in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Functional Mitral Regurgitation
- What is being tested?
- Dapagliflozin and guideline-directed medical therapy (GDMT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 3 sitesChina
- Study dates
- 1 Apr 2022to 31 Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
The Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510000
Zhuoshan Huang, Dr, 86 85252168, huangzhsh3@mail.sysu.edu.cn
- Recruiting
The First Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510620
Xiaodong Zhuang, Dr, +86 02087338190, zhuangxd3@mail.sysu.edu.cn
- Recruiting
The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital
Meizhou, Guangdong, 514799
Jinlai Liu, Prof, 13503060663, liujinl@mail.sysu.edu.cn
About this study
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).
Read the 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
- Conditions
- Functional Mitral Regurgitation
- Being tested
- Dapagliflozin, guideline-directed medical therapy (GDMT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
dapagliflozin 10mg once daily for 3 months after randomization
guideline-directed medical therapy (GDMT)Other
guideline-directed medical therapy (GDMT)
| Study group | Role | What they receive |
|---|---|---|
| dapagliflozin group | Experimental | GDMT and dapagliflozin 10mg once daily Receives: Drug: Dapagliflozin; Other: guideline-directed medical therapy (GDMT) |
| control group | Active comparator | GDMT only Receives: Other: guideline-directed medical therapy (GDMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
EROA of FMR
Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up
Measured: 3 months
Secondary outcomes (3)
cardiac structure
Change in RV measured by echocardiography from baseline to 12 weeks follow-up
Measured: 3 months
MACE
Occurrence of MACE in 12 weeks follow-up
Measured: 3 months
cardiac function
Change in serum NT-proBNP levels from baseline to 12 weeks follow-up
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2022
- Study start1 Apr 2022
- Primary completion30 Jun 2023 (estimated)
- Study completion31 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Functional Mitral RegurgitationStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiao-dong Zhuang, Sun Yat-sen University
- Investigators
- Xiaodong Zhuang, Dr, Study chair, First Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05606718
- Sponsor's protocol ID
- DEFORM trial
- Acronym
- DEFORM
- Status last verified
- Feb 2023
- First submitted
- 30 Oct 2022
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dapagliflozin Effect on FunctiOnal Mitral Regurgitation and Myocardial Remodeling
- ClinicalTrials.gov ID
- NCT05606718
- Acronym / sponsor ID
- DEFORM / DEFORM trial
- Conditions
- Functional Mitral Regurgitation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 31 Jul 2023 (estimated)
- First posted
- 7 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dapagliflozin group | Experimental | Drug: Dapagliflozin, Other: guideline-directed medical therapy (GDMT)GDMT and dapagliflozin 10mg once daily |
| control group | Active comparator | Other: guideline-directed medical therapy (GDMT)GDMT only |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozindapagliflozin 10mg once daily for 3 months after randomization | Drug | dapagliflozin group |
| guideline-directed medical therapy (GDMT)guideline-directed medical therapy (GDMT) | Other | control group, dapagliflozin group |
Primary outcome
EROA of FMR
Time frame: 3 months
Change in EROA of mitral regurgitation evaluated by echocardiography from baseline to 12 weeks follow-up
3 secondary outcomes
cardiac structure
Time frame: 3 months
MACE
Time frame: 3 months
cardiac function
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaodong Zhuang, Dr study chair
First Affiliated Hospital, Sun Yat-Sen University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin and guideline-directed medical therapy (GDMT) in people with Functional Mitral Regurgitation, run by Sun Yat-sen University at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaodong Zhuang, Dr (+86 02087338190, zhuangxd3@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EROA of FMR (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.