Mitral Regurgitation FunctionalNCT07197021
TEER In dynaMic sEvere Functional Mitral Regurgitation (TIMER)
A study testing TEER and GDMT in people with Mitral Regurgitation Functional, run by Sun Yat-sen University at 1 site in China.
Trial summary
Functional mitral regurgitation is a highly dynamic disease. Some patients exhibit only moderate(2+) functional mitral regurgitation at rest, which deteriorates to moderate-to-severe or severe FMR(3+ or 4+) during stress-termed dynamic severe functional mitral regurgitation. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Mitral Regurgitation Functional
- What is being tested?
- TEER and GDMT
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 540 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2027to 31 Dec 2034
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Clinically significant functional mitral regurgitation (MR (2+) at rest that deteriorates to moderate-to-severe (3+) or severe (4+) FMR during standardized handgrip stress echocardiography, with ΔEROA ≥0.1cm²) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
- Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization.
- Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 days preceding randomization
- Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
- Left ventricular ejection fraction (LVEF) of ≥ 20% Note: LVEF needs to be determined by one of the following methods: transthoracic echocardiography (TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance) within 90 days prior to randomization
- Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness
Who cannot join
- Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).
- Status 1 heart transplant or prior orthotropic heart transplantation.
- Introduction of a new heart failure drug class within the last 2 weeks prior to randomization.
- Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.
- Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD)) within 90 day prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization.
- Need for any cardiovascular surgery.
Show all 10Show fewer
- Mitral valve surgery is considered the preferred therapeutic option for the subject
- Renal replacement therapy
- 6-Minute Walk Test (6MWT) distance > 475 meters
- Mitral Valve Area (MVA) by planimetry < 4.0 cm2; if MVA by planimetry is not measurable, pressure half-time measurement is acceptable; MVA must be confirmed by the Echocardiography Core Laboratory
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080
Xiaodong Zhuang, 020-89998001, zhuangxd3@mail.sysu.edu.cn
About this study
Official title: TEER In dynaMic sEvere Functional Mitral Regurgitation：A Multicenter, Randomized, Controlled Trial
Functional mitral regurgitation is a highly dynamic disease. Some patients exhibit only moderate(2+) functional mitral regurgitation at rest, which deteriorates to moderate-to-severe or severe FMR(3+ or 4+) during stress-termed dynamic severe functional mitral regurgitation. Observational studies link this condition to worse outcomes, with mitral valve intervention offering potential benefits; however, high-quality evidence remains lacking.
The Transcatheter Edge-to-Edge Repair In DynaMic sEvere Functional Mitral Regurgitation trial aims to assess the safety and effectiveness of transcatheter edge-to-edge repair plus guideline-directed medical therapy versus guideline-directed medical therapy alone in symptomatic chronic heart failure patients with dynamic severe functional mitral regurgitation, defined as moderate regurgitation at rest deteriorating to severe during handgrip stress echocardiography.
Read more
This prospective, multi-center, randomized trial enrolls patients with dynamic severe functional mitral regurgitation confirmed by a core laboratory using handgrip stress echocardiography. Patients are randomized 1:1 to transcatheter edge-to-edge repair plus medical therapy or medical therapy alone. The primary endpoint is the composite of Cardiovascular death or heart failure hospitalization over the entire period.
This trial will provide critical evidence on transcatheter edge-to-edge repair in patients with dynamic severe functional mitral regurgitation, informing future treatment recommendations.
- Conditions
- Mitral Regurgitation Functional
- Being tested
- TEER, GDMT
- Keywords
- hand grip, TEER, dynamic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEERDevice
TEER
GDMTDrug
GDMT
| Study group | Role | What they receive |
|---|---|---|
| TEER+GDMT | Experimental | TEER +GDMT Receives: Device: TEER; Drug: GDMT |
| Control group | Placebo comparator | GDMT Receives: Drug: GDMT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of the recurrent composite of cardiovascular (CV) death and heart failure hospitalization (HFH) over the entire follow-up period (analyzed when the last subject completes 12 m of follow up).
Cardiovascular death or heart failure hospitalization (HFH) occurring within 2 years after enrollment
Measured: 2 years
Secondary outcomes (4)
Mitral Regurgitation (MR severity reduction to MR ≤2+ under stress) at 12 months
Mitral Regurgitation (MR severity reduction to MR <=2+) at 1 year, 2 years and 5 years
Measured: 5 years
Changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months.
KCCQ within 2 years and 5 years after enrollment
Measured: 5 years
Changes in 6-minute walk test (6MWT) distance at 12 months.
6MWT within 2 years and 5 years after enrollment
Measured: 5 years
Changes in NYHA functional class at 12 months.
NYHA
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2025
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mitral Regurgitation FunctionalStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 540 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07197021
- Sponsor's protocol ID
- TIMER
- Status last verified
- Sep 2026
- First submitted
- 20 Sep 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Giustino G, Camaj A, Kapadia SR, Kar S, Abraham WT, Lindenfeld J, Lim DS, Grayburn PA, Cohen DJ, Redfors B, Zhou Z, Pocock SJ, Asch FM, Mack MJ, Stone GW. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial. J Am Coll Cardiol. 2022 Nov 15;80(20):1857-1868. doi: 10.1016/j.jacc.2022.08.803.
PubMed 36357085Alachkar MN, Kirschfink A, Grebe J, Almalla M, Frick M, Milzi A, Moersen W, Becker M, Marx N, Altiok E. Dynamic handgrip exercise for the evaluation of mitral valve regurgitation: an echocardiographic study to identify exertion induced severe mitral regurgitation. Int J Cardiovasc Imaging. 2021 Mar;37(3):891-902. doi: 10.1007/s10554-020-02063-5. Epub 2020 Oct 16.
PubMed 33064244
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TEER In dynaMic sEvere Functional Mitral Regurgitation：A Multicenter, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT07197021
- Acronym / sponsor ID
- TIMER
- Conditions
- Mitral Regurgitation Functional
- Keywords
- hand grip, TEER, dynamic
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2034 (estimated)
- First posted
- 29 Sep 2025 (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 is a highly dynamic disease. Some patients exhibit only moderate(2+) functional mitral regurgitation at rest, which deteriorates to moderate-to-severe or severe FMR(3+ or 4+) during stress-termed dynamic severe functional mitral regurgitation. Observational studies link this condition to worse outcomes, with mitral valve intervention offering potential benefits; however, high-quality evidence remains lacking.
The Transcatheter Edge-to-Edge Repair In DynaMic sEvere Functional Mitral Regurgitation trial aims to assess the safety and effectiveness of transcatheter edge-to-edge repair plus guideline-directed medical therapy versus guideline-directed medical therapy alone in symptomatic chronic heart failure patients with dynamic severe functional mitral regurgitation, defined as moderate regurgitation at rest deteriorating to severe during handgrip stress echocardiography.
This prospective, multi-center, randomized trial enrolls patients with dynamic severe functional mitral regurgitation confirmed by a core laboratory using handgrip stress echocardiography. Patients are randomized 1:1 to transcatheter edge-to-edge repair plus medical therapy or medical therapy alone. The primary endpoint is the composite of Cardiovascular death or heart failure hospitalization over the entire period.
This trial will provide critical evidence on transcatheter edge-to-edge repair in patients with dynamic severe functional mitral regurgitation, informing future treatment recommendations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEER+GDMT | Experimental | Device: TEER, Drug: GDMTTEER +GDMT |
| Control group | Placebo comparator | Drug: GDMTGDMT |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinically significant functional mitral regurgitation (MR (2+) at rest that deteriorates to moderate-to-severe (3+) or severe (4+) FMR during standardized handgrip stress echocardiography, with ΔEROA ≥0.1cm²) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
- Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization.
- Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 days preceding randomization
- Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
- Left ventricular ejection fraction (LVEF) of ≥ 20% Note: LVEF needs to be determined by one of the following methods: transthoracic echocardiography (TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance) within 90 days prior to randomization
Key exclusion criteria (10 listed)
- Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).
- Status 1 heart transplant or prior orthotropic heart transplantation.
- Introduction of a new heart failure drug class within the last 2 weeks prior to randomization.
- Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.
- Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD)) within 90 day prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization.
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 |
|---|---|---|
| TEERTEER | Device | TEER+GDMT |
| GDMTGDMT | Drug | Control group, TEER+GDMT |
Primary outcome
The rate of the recurrent composite of cardiovascular (CV) death and heart failure hospitalization (HFH) over the entire follow-up period (analyzed when the last subject completes 12 m of follow up).
Time frame: 2 years
Cardiovascular death or heart failure hospitalization (HFH) occurring within 2 years after enrollment
4 secondary outcomes
Mitral Regurgitation (MR severity reduction to MR ≤2+ under stress) at 12 months
Time frame: 5 years
Changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months.
Time frame: 5 years
Changes in 6-minute walk test (6MWT) distance at 12 months.
Time frame: 5 years
Changes in NYHA functional class at 12 months.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Results publication: PubMed 36357085Giustino G, Camaj A, Kapadia SR, Kar S, Abraham WT, Lindenfeld J, Lim DS, Grayburn PA, Cohen DJ, Redfors B, Zhou Z, Pocock SJ, Asch FM, Mack MJ, Stone GW. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial. J Am Coll Cardiol. 2022 Nov 15;80(20):1857-1868. doi: 10.1016/j.jacc.2022.08.803.
- Results publication: PubMed 33064244Alachkar MN, Kirschfink A, Grebe J, Almalla M, Frick M, Milzi A, Moersen W, Becker M, Marx N, Altiok E. Dynamic handgrip exercise for the evaluation of mitral valve regurgitation: an echocardiographic study to identify exertion induced severe mitral regurgitation. Int J Cardiovasc Imaging. 2021 Mar;37(3):891-902. doi: 10.1007/s10554-020-02063-5. Epub 2020 Oct 16.
- Individual participant dataSharing planned: Yes
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TEER and GDMT in people with Mitral Regurgitation Functional, run by Sun Yat-sen University at 1 site 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 6 inclusion and 10 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: opening soon, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiaodong Zhuang, MD (020-89998001, 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?
The rate of the recurrent composite of cardiovascular (CV) death and heart failure hospitalization (HFH) over the entire follow-up period (analyzed when the last subject completes 12 m of follow up). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07197021, which also lists 2 linked publications.
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 4 Sep 2026.