Functional Mitral Regurgitation, Mitral Insufficiency, Mitral Regurgitation
Conditions
Keywords
Edwards Cardioband, Mitral Valve, Transcatheter, Mitral repair, Functional mitral regurgitation, Secondary mitral regurgitation, Annuloplasty
Brief summary
To establish the safety and effectiveness of the Edwards Cardioband System in patients with functional mitral regurgitation (FMR).
Detailed description
The ACTIVE Trial is a prospective, randomized, multicenter trial. Patients with clinically significant functional mitral regurgitation will be randomized 2:1 to receive either transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT) or GDMT alone. Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 5 years.
Interventions
Transcatheter mitral valve repair with the Edwards Cardioband System
GDMT Only
Sponsors
Edwards Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years; * Clinically Significant Functional Mitral Regurgitation (MR); * Symptomatic heart failure; * Patient hospitalized due to heart failure during 12 months prior to submission to Central Screening Committee OR elevated Brain Natriuretic Peptid (BNP); * Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow-up visit compliance.
Exclusion criteria
* Primarily degenerative MR; * Mitral annular calcification that would impede implantation of device; * Other severe valve disorders requiring intervention; * Mitral valve anatomy which may preclude proper Edwards Cardioband deployment; * Life expectancy of less than twelve months; * Patient is participating in concomitant research studies of investigational products which have not reached their primary endpoint; * Unwillingness or inability to undergo follow-up investigations/visits; * Other medical, social, or psychological conditions that precludes appropriate consent and follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of MR ≤ 2+ and Hierarchical Comparison of Randomized Device and Randomized Control Groups [Cardiovascular Death, Number of Heart Failure Hospitalizations, Improvement in 6 MWT Distance (in Meters) and KCCQ (Number of Points Improved)]. | 1 year | Hierarchical comparison of device and control groups (for randomized groups): MR ≤ 2+ and cardiovascular death, number of heart failure hospitalizations, improvement in 6 MWT distance (in meters) and KCCQ (number of points improved). |
| Number of Participants With Major Adverse Events (MAE) [Device Group Only] | 30 days | Overall rate of device and procedure related Major Adverse Events (MAEs) through 30 days post procedure (including death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention, and access site and vascular complications requiring intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device Success | 30 days | Device is deployed as intended and the delivery system is successfully retrieved as intended at the time of the patient's exit from the cardiac catheterization laboratory (per device analysis). |
| Secondary Safety Endpoints [Device Group Only] | 30 days | Components will be calculated with 95% confidence intervals 1. Death 2. Stroke 3. Myocardial infarction 4. Pericardial effusion requiring drainage 5. Mitral valve reintervention 6. Access site and vascular complications requiring intervention 7. Left circumflex coronary artery injury requiring intervention 8. Need for a new permanent pacemaker |
| Clinical Success | 30 days | Procedural success with evidence of MR reduction ≤ MR2+ and without MAEs\* at 30 days (per patient analysis). \*Major adverse events (MAE) defined as death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention and access site and vascular complications requiring intervention. |
| Procedural Success | 30 days | Device success with evidence of MR reduction to ≤ MR2+ at discharge and without the need for a surgical or percutaneous intervention prior to hospital discharge (per patient analysis). |
| Secondary Endpoints Through 1 Year (Powered for Randomized Arms Only) | 1 year | The following key secondary efficacy endpoints will be tested in comparison to control in a hierarchical order to preserve statistical power. 1. MR ≤ 1+ 2. NYHA Class 3. Kansas City Cardiomyopathy Questionnaire (KCCQ) 4. 6 Minute Walk Test (6MWT) 5. SF-36v2 Health Survey (SF-36) 6. Heart Failure Hospitalizations 7. Cardiovascular mortality |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roll-in Transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT). This patient group is treated by physicians requiring additional training prior to beginning randomized cohort enrollment. | 12 |
| Experimental: Edwards Cardioband System Transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT) | 0 |
| Control: No Intervention Guideline directed medical therapy (GDMT) | 0 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| At 2 Year Follow-up | Death | 1 | 0 | 0 |
| At 30 Days Follow-up | Subject is a Screen failure | 1 | 0 | 0 |
| At 3 Year Follow-up | Death | 1 | 0 | 0 |
| At 3 Year Follow-up | Withdrawal by Subject | 1 | 0 | 0 |
| At 4-year Follow-up | Exited Study for other reasons | 1 | 0 | 0 |
| At 6 Months Follow-up | Aborted implant | 1 | 0 | 0 |
| At 6 Months Follow-up | Death | 2 | 0 | 0 |
| At 6 Months Follow-up | Re-attempt procedure | 1 | 0 | 0 |
| At 6 Months Follow-up | Subject withdrawn by investigator | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Roll-in | Total |
|---|---|---|
| Age, Continuous | 71.8 years STANDARD_DEVIATION 9.6 | 71.8 years STANDARD_DEVIATION 9.6 |
| NYHA Functional Class Class 1 | 0 Participants | 0 Participants |
| NYHA Functional Class Class II | 5 Participants | 5 Participants |
| NYHA Functional Class Class III | 6 Participants | 6 Participants |
| NYHA Functional Class Class IV | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants |
| Region of Enrollment United States | 12 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 12 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 8 / 12 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 9 / 12 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants With Major Adverse Events (MAE) [Device Group Only]
Overall rate of device and procedure related Major Adverse Events (MAEs) through 30 days post procedure (including death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention, and access site and vascular complications requiring intervention
Time frame: 30 days
Population: No patients were randomized, therefore no data was collected in the randomized phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Edwards Cardioband System | Number of Participants With Major Adverse Events (MAE) [Device Group Only] | 0 Participants |
Primary
Prevalence of MR ≤ 2+ and Hierarchical Comparison of Randomized Device and Randomized Control Groups [Cardiovascular Death, Number of Heart Failure Hospitalizations, Improvement in 6 MWT Distance (in Meters) and KCCQ (Number of Points Improved)].
Hierarchical comparison of device and control groups (for randomized groups): MR ≤ 2+ and cardiovascular death, number of heart failure hospitalizations, improvement in 6 MWT distance (in meters) and KCCQ (number of points improved).
Time frame: 1 year
Population: No patients were randomized, therefore no data was collected. This parameter is meant to be analyzed in hierarchical order for the randomized arms only.
Secondary
Clinical Success
Procedural success with evidence of MR reduction ≤ MR2+ and without MAEs\* at 30 days (per patient analysis). \*Major adverse events (MAE) defined as death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention and access site and vascular complications requiring intervention.
Time frame: 30 days
Population: No patients were randomized, therefore no data was collected in the randomized phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Edwards Cardioband System | Clinical Success | 7 Participants |
Secondary
Device Success
Device is deployed as intended and the delivery system is successfully retrieved as intended at the time of the patient's exit from the cardiac catheterization laboratory (per device analysis).
Time frame: 30 days
Population: No patients were randomized, therefore no data was collected in the randomized phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Edwards Cardioband System | Device Success | 8 Participants |
Secondary
Procedural Success
Device success with evidence of MR reduction to ≤ MR2+ at discharge and without the need for a surgical or percutaneous intervention prior to hospital discharge (per patient analysis).
Time frame: 30 days
Population: No patients were randomized, therefore no data was collected in the randomized phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Edwards Cardioband System | Procedural Success | 7 Participants |
Secondary
Secondary Endpoints Through 1 Year (Powered for Randomized Arms Only)
The following key secondary efficacy endpoints will be tested in comparison to control in a hierarchical order to preserve statistical power. 1. MR ≤ 1+ 2. NYHA Class 3. Kansas City Cardiomyopathy Questionnaire (KCCQ) 4. 6 Minute Walk Test (6MWT) 5. SF-36v2 Health Survey (SF-36) 6. Heart Failure Hospitalizations 7. Cardiovascular mortality
Time frame: 1 year
Population: No patients were randomized, therefore no data was collected. The parameter is meant to be analyzed in hierarchical order for the randomized arms only.
Secondary
Secondary Safety Endpoints [Device Group Only]
Components will be calculated with 95% confidence intervals 1. Death 2. Stroke 3. Myocardial infarction 4. Pericardial effusion requiring drainage 5. Mitral valve reintervention 6. Access site and vascular complications requiring intervention 7. Left circumflex coronary artery injury requiring intervention 8. Need for a new permanent pacemaker
Time frame: 30 days
Population: No patients were randomized, therefore no data was collected
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Edwards Cardioband System | Secondary Safety Endpoints [Device Group Only] | 0 Participants |