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CardiomyopathyIMPROVE-FMRNCT03366649

Improving Mitral Repair for Functional Mitral Regurgitation

A study testing Undersizing Mitral Annuloplasty and Papillary Muscle Approximation in people with Cardiomyopathy and Cardiovascular Diseases, run by Emory University at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The investigators are interested in determining the best surgical technique to correct functional mitral regurgitation, as there is currently not one technique that is established to work better than the other. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Undersizing Mitral Annuloplasty and Papillary Muscle Approximation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
3 sitesUnited States
Study dates
20 Mar 2018to 31 Dec 2023
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Mitral regurgitation of moderate or greater severity, as defined by the guidelines of the American Society of Echocardiography (via a transthoracic echo)
  • Cardiomyopathy of ischemic or non-ischemic origins, with or without the need for coronary revascularization
  • Concomitant right-sided valve repair or replacement (i.e. patients requiring concomitant tricuspid procedures)
  • Able to sign informed consent and release of medical information forms

Who cannot join

  • Any evidence of structural (chordal or leaflet) mitral lesions
  • Prior mitral valve repair
  • Contraindication for cardiopulmonary bypass
  • Clinical signs of cardiogenic shock at the time of randomization
  • ST-segment elevation myocardial infarction within 14 days before inclusion in this study
  • Congenital heart disease, except patent foramen ovale (PFO) or atrial septal defect (ASD)
Show all 9Show fewer
  • Chronic renal insufficiency defined by creatinine ≥ 3.0 or chronic renal replacement therapy, who are contraindicated for cardiac surgery
  • Recent history of psychiatric disease that is likely to impair compliance with the study protocol, in the judgement of the investigator
  • Pregnancy at the time of randomization

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Emory St. Joseph's Hospital

    Atlanta, Georgia, 30342

Other trials in United States

About this study

The investigators are interested in determining the best surgical technique to correct functional mitral regurgitation, as there is currently not one technique that is established to work better than the other.

The technique used in current clinical practice is undersizing mitral annuloplasty (UMA), in which a prosthetic ring is implanted onto the mitral valve to correct the leakage. Though widely adopted, durability of the repair is less, as 58% of the patients present with recurrent FMR within 2 years. There are no specific algorithms to predict who might have UMA failure, but research indicates that some geometric indices might be strong predictors. The investigators are interested in testing the hypothesis that, elevated lateral inter-papillary muscle separation (IPMS) is a predictor of post-UMA recurrence of FMR at 12 months. In the first part of this study, the study team will measure lateral IPMS before surgery and relate to post-surgery FMR severity at discharge/30 days, 6 months and 12 months.

A relatively newer technique is papillary muscle approximation (PMA), in which a suture draws together the two muscles that connect the mitral valve to the heart muscle prior to performing UMA. This reduces the lateral inter-papillary muscle separation (IPMS) and is expected to improve the durability of UMA. In the second part of this study, the investigators will perform PMA and UMA together and determine if FMR severity is reduced at discharge/30 days, 6 months and 12 months.

Read the detailed description

Functional mitral regurgitation (FMR) is a common heart valve lesion that is observed in patients suffering for cardiomyopathies. Timely surgical repair of FMR can reduce volume overload and potentially improve cardiac function. Durable surgical techniques for FMR repair are lacking. Undersizing mitral annuloplasty (UMA) is the current technique of choice, but its durability is quite poor. Thirty five percent of the repairs fail within one year and 58% fail within 2 years.

One of the probable mechanisms causing UMA failure is elevated lateral inter-papillary muscle separation (IPMS). The study investigators are interested in understanding if the extent of lateral IPMS has a direct impact on the failure rates of UMA at 1 year post surgery. Secondly, the investigators are interested in determining if patients with elevated lateral IPMS benefit from papillary muscle approximation (PMA) along with UMA.

The investigators are interested in determining the best way to correct functional mitral regurgitation, as there is currently not one technique that is established to better than the other. The most common repair technique is called undersizing mitral annuloplasty (UMA), in which a prosthetic ring is implanted onto the mitral valve to correct the leakage. Another more recent technique is papillary muscle approximation (PMA), in which a suture draws together the two muscles that connect the mitral valve to the heart muscle prior to performing UMA. In this research study, the study team is investigating whether they can identify those patients who will benefit from one repair over another.

The primary objective of this protocol is to investigate if pre-operative IPMS is predictive of FMR severity at 12 months after UMA to repair FMR. Furthermore, whether a cut-off value of pre-operative inter-papillary muscle separation can be established to predict patients who might have failure of UMA.

The secondary objective of this protocol is to investigate if adding PMA to UMA is an effective technique in reducing recurrence of FMR at 12 months post-procedure.

Being tested
Undersizing Mitral Annuloplasty, Papillary Muscle Approximation
Keywords
Bypass Surgery, Cardiology, Coronary Artery Bypass Surgery, Mitral Valve Repair, Mitral Valve Surgery, Coronary Revascularization
Medical subject headings
Cardiomyopathies, Cardiovascular Diseases, Heart Failure, Coronary Artery Disease, Heart Diseases, Heart Valve Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Undersizing Mitral AnnuloplastyProcedure or surgery

    Participants will receive a commercially available annuloplasty ring of the surgeon's choice. Sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size.

  • Papillary Muscle ApproximationProcedure or surgery

    One or two 4-0 pledgeted sutures are used to draw the two papillary muscle tips together to reduce the inter papillary muscle separation (IPMS) before undergoing undersizing mitral annuloplasty.

Study groups in NCT03366649
Study groupRoleWhat they receive
UMA (Group 1)OtherParticipants in the UMA group will receive an undersizing mitral annuloplasty (UMA).
Receives: Procedure: Undersizing Mitral Annuloplasty
UMA + PMA (Group 2)OtherParticipants in the UMA + PMA group will receive an undersizing mitral annuloplasty (UMA) with papillary muscle approximation (PMA).
Receives: Procedure: Undersizing Mitral Annuloplasty; Procedure: Papillary Muscle Approximation
Retrospectively identified patientsNo interventionRetrospectively identified patients, who already underwent the standard of care surgery for the lesion of interest at Emory, within 6 months (± 1 month) after the date of their surgery, and are suitable for recruitment to the study for their post-operative research.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in FMR Severity

    The Severity (grade 0 to 4+) of mitral regurgitation of mitral regurgitation is measured using cardiac echocardiography and/or MRI (per physician's discretion).

    Grade 0: None Grade 1 (Mild): Small, restricted jet of regurgitation with minimal impact on the heart's function. Typically, no symptoms and normal or near-normal left ventricular function.

    Grade 2 (Moderate): Moderate jet size with some effect on the heart, but symptoms may still be absent or minimal. Mild to moderate left ventricular dilation may be present.

    Grade 3 (Moderately Severe): Larger jet, more significant regurgitation, potentially causing mild heart failure symptoms or moderate dilation of the left ventricle.

    Grade 4 (Severe): A large, prominent jet of regurgitation that significantly impacts heart function, often resulting in severe symptoms and marked left ventricular dilation.

    Measured: Pre-Intervention and Post-Intervention (12 Months)

Secondary outcomes (10)

  1. Mortality Rate

    The number of participants who are deceased will be collected throughout the study at discharge and planned follow up visits.

    Measured: Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)

  2. Number of Major Adverse Cardiac Events (MACE)

    MACE is defined as a composite of clinical events comprised of the following:

    • Death
    • Stroke
    • Worsening heart failure (+1 New York Heart Association (NYHA) class)
    • Congestive heart failure (CHF) hospitalization
    • Mitral valve re-intervention

    Measured: Up to 12 months post -intervention

  3. Change in Quality-of-Life Scale Score

    Participants will be asked to measure their perceived quality of life on a scale from 0 to 100 where 0 indicates "worst imaginable health state" and 100 indicates "best imaginable health state".

    Measured: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)

  4. Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score

    The Minnesota Living with Heart Failure Questionnaire is a 21-item questionnaire that asks participants to describe how much their heart failure has affected life during the past month (4 weeks). Participants are asked if their heart failure prevented them from living as they want when completing daily tasks. Responses are rated on a scale from 0 to 5; 0 represents "no", 1 represents "very little" and 5 represents "very much" on a continuum. The MLHF score is obtained by summing the subjects responses. A minimum score is 0 indicating no affect to life and a maximum score is 105 indicating the greatest affect to life.

    Measured: Baseline, Post-Intervention (Month 12)

  5. Change in Functional Status Assessed by 6-Minute Walk Test (6MWT)

    Functional status will be measured by a 6-minute walk test, which assesses the distance walked (in feet) on a flat, hard surface in a period of 6 minutes (the 6MWD). The test is used for preoperative and postoperative evaluation and for measuring the response to therapeutic interventions for pulmonary and cardiac disease. Optimal reference equations from healthy population-based samples using standardized 6MWT methods are not yet available. A low 6MWD is nonspecific and nondiagnostic. When the 6MWD is reduced, a thorough search for the cause of the impairment is warranted.

    Measured: Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)

  6. All Cause Readmission Rate

    Readmission rate will be calculated for any cause within the first 30 days following surgery throughout the duration of the study.

    Measured: Post Surgery (Up to 30 Days)

  7. Heart Failure Readmission Rate

    Readmission rate will be calculated for heart failure after 30 days following surgery throughout the duration of the study. Classification of readmission as heart failure related requires at least 2 out of the following signs and symptoms of acute decompensated heart failure:

    • Dyspnea felt related to HF
    • Treatment with intravenous diuretic, vasodilator or inotropic therapy
    • X ray evidence of pulmonary edema or pulmonary vascular congestion
    • Rales on physical exam
    • Pulmonary capillary wedge pressure (PCWP) or LVEDP > 18mm Hg

    Measured: Post Surgery (Up to 30 Days)

  8. Change in Left Ventricular Volume

    Change in left ventricular volume at 6- and 12-month post-intervention compared to baseline as measured by as measured by the left ventricular end-diastolic diameter determined by echocardiogram.

    Measured: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)

  9. Change in Ejection Fraction

    Change in left ventricular ejection fraction at 12- months post-intervention compared to baseline as measured by echocardiogram.

    Measured: Baseline, Post-Intervention (Month 12)

  10. Change in Left Ventricular Mass

    Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.

    Measured: Baseline, Post-Intervention (Month 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2017
  2. Study start20 Mar 2018
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2023

Why it stopped: The study was terminated due to poor enrollment during COVID-19, which also hindered postoperative testing. With insufficient enrollment to meet trial goals, funds were redirected to animal studies on the same clinical issues.

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03366649
Sponsor's protocol ID
IRB00097939
Other IDs
1R01HL133667-01A1
Acronym
IMPROVE-FMR
Status last verified
Dec 2024
First submitted
30 Nov 2017
Last updated
16 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kalra K, Wang Q, McIver BV, Shi W, Guyton RA, Sun W, Sarin EL, Thourani VH, Padala M. Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation. J Am Coll Cardiol. 2014 Nov 4;64(18):1867-79. doi: 10.1016/j.jacc.2014.07.988. Epub 2014 Oct 27.

    PubMed 25444139

  • Michler RE, Smith PK, Parides MK, Ailawadi G, Thourani V, Moskowitz AJ, Acker MA, Hung JW, Chang HL, Perrault LP, Gillinov AM, Argenziano M, Bagiella E, Overbey JR, Moquete EG, Gupta LN, Miller MA, Taddei-Peters WC, Jeffries N, Weisel RD, Rose EA, Gammie JS, DeRose JJ Jr, Puskas JD, Dagenais F, Burks SG, El-Hamamsy I, Milano CA, Atluri P, Voisine P, O'Gara PT, Gelijns AC; CTSN. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med. 2016 May 19;374(20):1932-41. doi: 10.1056/NEJMoa1602003. Epub 2016 Apr 3.

    PubMed 27040451

  • Kron IL, Hung J, Overbey JR, Bouchard D, Gelijns AC, Moskowitz AJ, Voisine P, O'Gara PT, Argenziano M, Michler RE, Gillinov M, Puskas JD, Gammie JS, Mack MJ, Smith PK, Sai-Sudhakar C, Gardner TJ, Ailawadi G, Zeng X, O'Sullivan K, Parides MK, Swayze R, Thourani V, Rose EA, Perrault LP, Acker MA; CTSN Investigators. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg. 2015 Mar;149(3):752-61.e1. doi: 10.1016/j.jtcvs.2014.10.120. Epub 2014 Nov 6.

    PubMed 25500293

  • Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, Smith PK, Hung JW, Blackstone EH, Puskas JD, Argenziano M, Gammie JS, Mack M, Ascheim DD, Bagiella E, Moquete EG, Ferguson TB, Horvath KA, Geller NL, Miller MA, Woo YJ, D'Alessandro DA, Ailawadi G, Dagenais F, Gardner TJ, O'Gara PT, Michler RE, Kron IL; CTSN. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med. 2014 Jan 2;370(1):23-32. doi: 10.1056/NEJMoa1312808. Epub 2013 Nov 18.

    PubMed 24245543

Questions about this trial

What is this clinical trial studying?

A study testing Undersizing Mitral Annuloplasty and Papillary Muscle Approximation in people with Cardiomyopathy and Cardiovascular Diseases, run by Emory University at 3 sites in United States.

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: stopped early, as of the sponsor's last update on 16 Jan 2025. 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 United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in FMR Severity (time frame: Pre-Intervention and Post-Intervention (12 Months)). 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 NCT03366649, which also lists 4 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 16 Jan 2025.

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