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NCT03366649: IMPROVE-FMR

Improving Mitral Repair for Functional Mitral Regurgitation

Terminated NA Results posted Last updated 16 January 2025
What this trial tests

NA trial testing Undersizing Mitral Annuloplasty in Cardiomyopathy in 34 participants. Terminated before completion.

Timeline
20 March 2018
Primary endpoint
31 December 2023
31 December 2023

Quick facts

Lead sponsorEmory University
PhaseNA
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment34
Start date20 March 2018
Primary completion31 December 2023
Estimated completion31 December 2023
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Emory University

Who can join

18 and older, any sex, with Cardiomyopathy or Cardiovascular Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in FMR Severity Primary · Pre-Intervention and Post-Intervention (12 Months)

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,

Baseline
GroupValue95% CI
UMA (Group 1)2.7± 0.8
12 months post-intervention
GroupValue95% CI
UMA (Group 1)0.7± 0.7
Mortality Rate Secondary · Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)

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

up to 20 days post-Intervention
GroupValue95% CI
UMA (Group 1)0
12 months post-intervention
GroupValue95% CI
UMA (Group 1)0
Number of Major Adverse Cardiac Events (MACE) Secondary · Up to 12 months post -intervention

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

Congestive heart failure (CHF) hospitalization
GroupValue95% CI
UMA (Group 1)1
Death
GroupValue95% CI
UMA (Group 1)0
Mitral valve re-intervention
GroupValue95% CI
UMA (Group 1)0
Stroke
GroupValue95% CI
UMA (Group 1)0
Worsening heart failure (+1 New York Heart Association (NYHA) class)
GroupValue95% CI
UMA (Group 1)0
Change in Quality-of-Life Scale Score Secondary · Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)

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".

Baseline
GroupValue95% CI
UMA (Group 1)69.0± 19.0
Post-Intervention (Month 12)
GroupValue95% CI
UMA (Group 1)76.9± 16.9
Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score Secondary · Baseline, Post-Intervention (Month 12)

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

Baseline
GroupValue95% CI
UMA (Group 1)44.2± 31.3
12 months Post-Intervention
GroupValue95% CI
UMA (Group 1)30.9± 28.0
Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) Secondary · Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)

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.

Baseline
GroupValue95% CI
UMA (Group 1)1048.4± 293.7
12 months Post-Intervention
GroupValue95% CI
UMA (Group 1)1210.6± 203.6
All Cause Readmission Rate Secondary · Post Surgery (Up to 30 Days)

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

Post-Surgery (up to 30 days)
GroupValue95% CI
UMA (Group 1)2
Post-Surgery (30 days through 12 Months)
GroupValue95% CI
UMA (Group 1)4
Heart Failure Readmission Rate Secondary · Post Surgery (Up to 30 Days)

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

GroupValue95% CI
UMA (Group 1)0
Change in Left Ventricular Volume Secondary · Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)

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.

Baseline
GroupValue95% CI
UMA (Group 1)5.4± 0.8
12 months Post-Intervention
GroupValue95% CI
UMA (Group 1)4.8± 0.8
Change in Ejection Fraction Secondary · Baseline, Post-Intervention (Month 12)

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

Baseline
GroupValue95% CI
UMA (Group 1)45± 14
12 months post-intervention
GroupValue95% CI
UMA (Group 1)46± 14

Adverse events — posted to ClinicalTrials.gov

Time frame: Considering the observational nature of this study, and the absence of any experimental procedures, adverse event (AE) reporting was limited only to those events that occurred from the specific non-standard-of-care lab procedures that were performed at 6- and 12-month visits.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

UMA (Group 1)
Serious: 4/26 (15%)
Deaths: 0/26

Serious adverse events (4 terms)

ReactionSystemUMA (Group 1)
Atrial fibrillation + congestive heart failure (CHF)Cardiac disorders
Atrial FlutterCardiac disorders
Acute cholecystitis with perforated gallbladderGastrointestinal disorders
SyncopeGeneral disorders

Most-reported serious reactions: Atrial fibrillation + congestive heart failure (CHF), Atrial Flutter, Acute cholecystitis with perforated gallbladder, Syncope.

Data from ClinicalTrials.gov NCT03366649 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing