Noninferiority Trial of MitraClip Implantation Strategies: 1 Clip vs. 2 Clips in Patients With Functional Mitral Regurgitation

Study Overview
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Brief Summary
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Implantation of the MitraClip has become the most frequently used percutaneous technique to treat significant (grade 3+ or 4+) mitral regurgitation (MR) in elderly patients deemed inoperable or at high surgical risk. In Europe, about two-thirds of patients treated with the MitraClip suffer from MR of functional origin secondary to ischemic or dilated cardiomyopathy. At present, there is debate among operators on whether stabilizing/supporting a single adequately implanted clip with a second clip is beneficial for patients with functional MR.

Detailed Description
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Implantation of the MitraClip has become the most frequently used percutaneous technique to treat significant (grade 3+ or 4+) mitral regurgitation (MR) in elderly patients deemed inoperable or at high surgical risk. In Europe, about two-thirds of patients treated with the MitraClip suffer from MR of functional origin secondary to ischemic or dilated cardiomyopathy. At present, there is debate among operators on whether stabilizing/supporting a single adequately implanted clip with a second clip is beneficial for patients with functional MR. Purpose To demonstrate the noninferiority of a 1-clip strategy vs. a 2-clip strategy of MitraClip implantation, when the second clip in the 2-clip study arm is implanted for stabilizing/supporting purposes.

Official Title
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Noninferiority Trial of MitraClip Implantation Strategies: 1 Clip vs. 2 Clips in Patients With Functional Mitral Regurgitation (One-Plus-One)

Conditions
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Mitral Regurgitation Functional

Intervention / Treatment
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* Device: MitraClip implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Absence of a structural abnormality of the mitral valve giving rise to MR. MR severity of US grade 3+ or 4+ of central or noncentral origin Patient must consent to randomization in the hybrid operating theater upon successful implantation of a single MitraClip. Written informed consent must be provided prior to the MitraClip procedure. Exclusion Criteria: patients with primary regurgitation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multi-center, randomized, parallel-arm trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: One CLIP<br>Implantation of single MitraClip | Device: MitraClip implantation<br>* Device to approximate the mitral valve leaflets<br>|
| Active Comparator: Two CLIPs<br>Implantation of second MitraClip (after successful Implantation of single MitraClip) | Device: MitraClip implantation<br>* Device to approximate the mitral valve leaflets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of number of participants who died death within one year | death | 1 year | 
| Evaluation of number of rehospitalizations due to heart failure among patients receiving one or two clips | heart failure rehospitalization | 1 year | 
| Evaluation of number of participants with recurrent regurgitation within one year | recurrence of mitral regurgitation (>grade 2+ at 1 year) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death | freedom from death (1-year) | 1 year | 
| heart failure | freedom from heart failure (1-year) | 1 year | 
| rehospitalization | rehospitalization | 1-year | 
| regurgitation | freedom from recurrence of mitral regurgitation (>2+; 1-year) | 1-year | 
| success rate | procedural success rate in 2-clip arm | 1-year | 
| procedure duration | procedure duration | 1-year | 
| total device time | total device time | 1-year | 
| fluoroscopy time | fluoroscopy time | 1-year | 
| contrast volume | contrast volume | 1-year | 
| complications | periprocedural (30-day) complications | 1-year | 
| echocardiographic variables | The following echocardiographic variables will be assessed by 2-dimensional transthoracic echocardiography at 12 months: Left ventricular (LV) end-diastolic diameter and volume; LV end-systolic diameter and volume; LV ejection fraction; LV outflow tract diameter and velocity time integral in LV outflow tract (to calculate forward stroke volume). | 1-year | 
| changes in echocardiographic variables | Changes from baseline to 12 months in echocardiographically assessed (at both time points) LV end-diastolic diameter and volume; LV end-systolic diameter and volume; LV ejection fraction; and forward stroke volume. | 1-year | 
| NYHA | NYHA functional class | 1-year | 
| 6-minutes walk | 6-minutes walk distance | 1-year | 
| quality of life | Assessment of the Minnesota Living With Heart Failure Questionnaire (MLHFQ) quality-of-life score. The questionnaire consists of 21 quality-of-life questions to be answered by the patient on a grading scale of 0 (best) to 5 (worst). Thus, the overall MLHFQ score ranges from 0 to 105. | 1-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitral Regurgitation, transcatheter mitral valve repair, MitraClip