The objective of this prospective, multi-center, randomized, double-blind trial is to assess the safety and efficacy of the CARILLON Mitral Contour System in treating functional mitral regurgitation (FMR) associated with heart failure, compared to a…
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Vascular therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is to demonstrate a statistically significant
improvement in regurgitant volume associated with the CARILLON device at twelve
(12) months, relative to the Control population.
Secondary outcome
Safety: The following secondary safety endpoints will measure the effect of the
CARILLON Mitral Contour System on clinical safety parameters of interest,
relative to the Control population
To document the difference in the rate of major adverse events between
randomized groups, at 1 and 12-months post randomization.
Major Adverse Events are defined as a composite of the following:
- Death
- Myocardial Infarction
- Device Embolization
- Vessel Erosion, requiring percutaneous or surgical intervention
- Cardiac Perforation, requiring percutaneous or surgical intervention
- Occurrence of cardiac surgery or percutaneous coronary intervention
associated with device failure
* To assess the rate of heart failure hospitalizations (number of admissions,
and total associated days in the hospital), from the time of the index
procedure through twelve months of follow-up.
Efficacy: The following secondary efficacy endpoints will assess the effect of
the CARILLON Mitral Contour System on clinical parameters of interest, relative
to the Control population:
* To assess the change from baseline to twelve months for six-minute walk
distance
* To assess the change from baseline to twelve months in left ventricular
volumes (end diastolic and end systolic)
Background summary
'Heart Failure and Functional Mitral Regurgitation':
The mitral valve is a valve between the two chambers of the left side of the
heart (left atrium and left ventricle). The mitral valve opens and closes to
allow blood flow between these two portions of the heart. 'Functional mitral
regurgitation "occurs when the mitral valve becomes too large and not entirely
closes anymore. This occurs because the left ventricle (the heart chamber which
is responsible for pumping blood to the body) is increased. If the mitral valve
does not close all the way anymore, a small amount of blood leaks back with
each heartbeat (to the left atrium and lungs), causing the heart to pump blood
and to work harder to be able to pump the same amount of blood to the rest of
the body. By mitral regurgitation the heart starts to fail and patients
experience symptoms such as breathlessness, fatigue (constantly tired) and / or
concentration problems. This is called "heart failure".
The tool used in this medical research, the CARILLON Mitral Contour System®
(CMCS), will be used for the treatment of functional mitral regurgitation. The
purpose of this study is to continue the evaluation of the safety and long-term
efficacy of the CMCS in people with functional mitral regurgitation due to
heart failure.
Study objective
The objective of this prospective, multi-center, randomized, double-blind trial
is to assess the safety and efficacy of the CARILLON Mitral Contour System in
treating functional mitral regurgitation (FMR) associated with heart failure,
compared to a randomized Control group which is medically managed according to
heart failure guidelines.
Study design
The REDUCE FMR Trial is a prospective, multi-center, randomized, double-blind
clinical trial.
Subjects will be randomized between the Treatment Group and a Control Group.
Subjects will be randomized in a 3:1 ratio (Treatment : Control group).
The Treatment group will be implanted with the CARILLON device. The Control
group will be medically managed according to current heart failure guidelines
i,ii.
As this is a double-blinded study, both the patients (Treatment and Control
groups) and the assessors of key endpoints will be blinded for 12 months.
Subjects randomized to the Control or Treatment group will have safety and
efficacy assessments performed at baseline, one (1), six (6), and twelve (12)
months after randomization.
Subjects randomized to the Control group may be offered the CARILLON device
once they have completed the protocol defined follow-up period (Cross-Over
Registry).
Intervention
Placement of CARILLON device.
Study burden and risks
The major benefit of percutaneous treatment with the CARILLON Mitral Contour
System is a potential reduction in mitral regurgitation through a minimally
invasive treatment method, where no current minimally invasive treatment option
exists for these subjects. The major potential benefits include:
- Clinical reduction in mitral regurgitation with a non-surgical treatment
method
- Improvements in overall function including potential reduction of symptomps
associated with dilated cardiomyopathy/mitral regurgitation.
Risks associated with the CARILLON Mitral Contour System include those risks
associated with routine coronary angiography as well as those risks
predominantly associated with the delivery and permanent placement of the
CARILLON implant.
In summary, the rate of major adverse events seen in the TITAN trial (previous
trial with device) was comparable to or lower than the rate of major adverse
events reported and accepted with therapies that are commercially available and
offered to patients with moderate heart failure. The lower rate of MAEs is
consistent with the goals of a percutaneous therapy and is an important
benchmark for the risk-benefit equation.
Besides the procedure the patient has to come to the hospital for screening,
1M, 6M and 12M visit, which will take in total 8-12hours. After the procedure
the patient has to stay 1-2 nights in the hospital. The patient will have 5
venapuntions and 2 catherisations. Radiological exposure consists of
angiograms, venograms and cinefluoroscopy with a total exposure of 10mSv
throughout the whole study.
Two quality of life questionnaires at screening, 1M, 6M and 12M visit. Vital
signs will be assessed at every visit.
Lake Washington BLV 5540
Kirkland 98033 WA
US
Lake Washington BLV 5540
Kirkland 98033 WA
US
Listed location countries
Age
Inclusion criteria
For Main study :;1. Diagnosis of dilated ischemic or non-ischemic cardiomyopathy
2. Functional Mitral Regurgitation: - 2+ (Moderate), 3+ (Moderate/Severe), or 4+ (Severe)
3. NYHA II, III, or IV (refer to Appendix D for NYHA Classification)
4. Six Minute Walk distance of at least 150 meters and no farther than 450 meters
5. Subject meets anatomic screening criteria as determined by angiographic screening at the time of the index procedure to ensure that implant can be sized and placed in accordance with the Instructions for Use
6. Left Ventricular Ejection Fraction <= 50%
NOTE: Subjects with LVEF of 41- 50% can only be included if baseline
NYHA is class III/IV AND MR grade is 3+/4+ (moderately-severe/severe)
7. LV end diastolic dimension (LVEDD) >55mm or LVEDD/BSA >3.0cm/m2
8. Stable heart failure medication regimen for at least three (3) months (refer to Appendix G for definition of stable heart failure regimen)
9. Age >= 18 years old and <= 85 years old
10. The subject has read the informed consent, agrees to comply with the requirements, and has signed the informed consent to participate in the study
11. Female subjects of child-bearing potential must have a negative serum βHCG test;For Cross-Over registry :
1. Diagnosis of dilated ischemic or non-ischemic cardiomyopathy
2. Functional Mitral Regurgitation: - 2+ (Moderate), 3+ (Moderate/Severe), or 4+ (Severe)
3. NYHA II, III, or IV (refer to Appendix D for NYHA Classification)
4. Subject meets anatomic screening criteria as determined by angiographic screening at the time of the index procedure to ensure that implant can be sized and placed in accordance with the Instructions for Use
5. Left Ventricular Ejection Fraction <= 50%
NOTE: Subjects with LVEF of 41- 50% can only be included if baseline
NYHA is class III/IV AND MR grade is 3+/4+ (moderately-severe/severe)
6. LV end diastolic dimension (LVEDD) >55mm or LVEDD/BSA >3.0cm/m2
7. The subject has read the informed consent, agrees to comply with the requirements, and has signed the informed consent to participate in the study
8. Female subjects of child-bearing potential must have a negative serum βHCG test
Exclusion criteria
Main study :
1. Hospitalization in past three (3) months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina
2. Hospitalization in the past 30 days for coronary angioplasty or stent placement
3. Subjects expected to require any cardiac surgery, including surgery for coronary artery disease (unprotected left main stenosis greater than or equal to 50% or, greater than or equal to 70% stenosis in at least three (3) epicardial coronary arteries in the absence of prior bypass surgery), or for pulmonic, aortic, or tricuspid valve disease within one (1) year
4. Subjects with echocardiographic documentation of non-compaction cardiomyopathy with associated hypercontractility of the cardiac structures supporting the mitral annulus
5. Subjects expected to require any percutaneous coronary intervention within 30 days of enrollment
6. Recipient of intravenous positive-inotrope infusion or intra- aortic balloon pump support within the past 30 days
7. Presence of a mechanical mitral heart valve, mitral bio-prosthetic valve or mitral annuloplasty ring
8. Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV), or anticipated need for cardiac resynchronization therapy (CRT) within twelve (12) months
9. Presence of a coronary artery stent under the CS / GCV in the implant target zone
10. Significant organic mitral valve pathology (e.g., moderate or severe myxomatous degeneration, with or without mitral leaflet prolapse, rheumatic disease, full or partial chordal rupture)
11. Presence of severe mitral annular calcification
12. Presence of left atrial appendage (LAA) clot. Patients with a current/ongoing (documented within the last 12 months) history of atrial fibrillation must undergo a trans-esophageal echo prior to the procedure to rule-out left atrial appendage clot to minimize the risk of thromboembolism
caused by the tissue plication
13. Cerebral vascular event within the past three (3) months
14. Presence of primary renal dysfunction or significantly compromised renal function as reflected by a serum creatinine > 2.2 mg/dL (194.5 µmol/L) OR estimated Glomerular Filtration Rate (eGFR) < 30 ml/min
15. Allergy to contrast dye that cannot be pre-medicated
16. Inability to undertake a six-minute walk test due to physical restrictions/limitations
17. Chronic severe pathology limiting survival to less than 12-months
18. Anticipated need of left ventricular assist device within twelve (12) months
19. Currently participating in an investigational study that clinically interferes
with the current study endpoints.;Cross-over registry:
1. Hospitalization in past three (3) months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina
2. Hospitalization in the past 30 days for coronary angioplasty or stent placement
3. Subjects with echocardiographic documentation of non-compaction cardiomyopathy with associated hypercontractility of the cardiac structures supporting the mitral annulus
4. Subjects expected to require any percutaneous coronary intervention within 30 days of enrollment
5. Recipient of intravenous positive-inotrope infusion or intra- aortic balloon pump support within the past 30 days
6. Presence of a mechanical mitral heart valve, mitral bio-prosthetic valve or mitral annuloplasty ring
7. Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV)
8. Presence of a coronary artery stent under the CS / GCV in the implant target zone
9. Significant organic mitral valve pathology (e.g., moderate or severe myxomatous degeneration, with or without mitral leaflet prolapse, rheumatic disease, full or partial chordal rupture)
10. Presence of severe mitral annular calcification
11. Presence of left atrial appendage (LAA) clot. Patients with a current/ongoing (documented within the last 12 months) history of atrial fibrillation must undergo a trans-esophageal echo prior to the procedure to rule-out left atrial appendage clot to minimize the risk of thromboembolism
caused by the tissue plication
12. Cerebral vascular event within the past three (3) months
13. Presence of primary renal dysfunction or significantly compromised renal function as reflected by a serum creatinine > 2.2 mg/dL (194.5 µmol/L) OR estimated Glomerular Filtration Rate (eGFR) < 30 ml/min
14. Allergy to contrast dye that cannot be pre-medicated
15. Currently participating in an investigational study that clinically interferes
with the current study endpoints.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02325830 |
| CCMO | NL53064.068.15 |