A Clinical Evaluation of the Safety and Effectiveness of the MitraClip® System for the Treatment of Functional Mitral Regurgitation in Symptomatic Heart Failure Subjects (COAPT Recruitment Closed). COAPT CAS (Recruitment Closed)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Mitral Regurgitation
- Sponsor
- Abbott Medical Devices
- Enrollment
- 776
- Locations
- 85
- Primary Endpoint
- Primary Safety Endpoint - Percentage of Participants With Freedom From Device Related Complications at 12 Months
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial is to confirm the safety and effectiveness of the MitraClip System for the treatment of moderate-to-severe or severe functional mitral regurgitation (FMR) in Symptomatic Heart Failure Subjects who are treated per standard of care and who have been determined by the site's local heart team as not appropriate for mitral valve surgery. This randomized controlled trial will provide the opportunity to strengthen or add labeling claims regarding safety and clinical benefits of the MitraClip System for symptomatic heart failure patients with moderate-to-severe or severe functional mitral regurgitation.
Approximately 610 subjects will be randomized at up to 100 investigational sites with approximately 305 subjects targeted to receive the study device. COAPT study completed recruiting subjects in June 2017.
As part of the COAPT trial, a subset of patients will be registered in the cardiopulmonary exercise (CPX) sub-study. The objective of this sub-study is to evaluate the exercise responses in a sub-cohort of COAPT subjects who receive MitraClip device (Device group) compared to the Control group who do not receive MitraClip device. (Note: the CPX Sub-study subjects will contribute to the analyses of the COAPT primary and secondary endpoints)
As an extension of the COAPT RCT trial, COAPT CAS study will be conducted after COAPT enrollment is complete under the same investigational device exemption (IDE(G120024)). The objective of this study is to evaluate the MitraClip® NT System for the treatment of clinically significant functional mitral regurgitation (FMR) in symptomatic heart failure subjects who are treated per standard of care and who have been determined by the site's local heart team as not appropriate for mitral valve surgery. The anticipated Study Completion Date is July 2024. COAPT CAS completed recruiting subjects in March 2019.
Detailed Description
Prospective, randomized, parallel-controlled, multicenter clinical evaluation of the MitraClip device for the treatment of clinically significant functional mitral regurgitation in symptomatic heart failure subjects who are treated per standard of care and who have been determined by the site's local heart team as not appropriate for mitral valve surgery. Eligible subjects will be randomized in a 1:1 ratio to the MitraClip device (Device group) or to no MitraClip device (Control group). As part of the COAPT trial, a subset of patients (at least 50 up to 100 in total) will be registered in the CPX Sub-study, which is designed as a prospective, randomized (1:1 ratio to the MitraClip or no MitraClip device), parallel-controlled, multicenter study registering approximately 50-100 subjects in up to 50 qualified US sites from the COAPT trial. Subjects registered and randomized in the CPX Sub-study will contribute to the total enrollment approximately of 610 subjects in the COAPT trial. Roll-in subjects will not participate in the CPX Sub-study. The COAPT CAS study is designed as a prospective, multicenter, single arm, continued access registry study. A maximum of 800 subjects (anticipated) will be registered from up to 75 sites in the United States. The enrollment will end once pre-market approval (PMA) of the proposed expanded indication of MitraClip System is obtained. Active follow-up of patients will be performed through 12 months with scheduled visits at 30 days and 12 months. The national Trans catheter Valve Therapy Registry (TVT Registry) will be used for data collection through 12 months. Annual follow-up data from 2 years through year 5 post-implant will be obtained by linkage to the Centers for Medicare and Medicaid Services (CMS) Claims database. COAPT CAS data may be used to support the PMA application of the labeling claims for the treatment of moderate to severe or severe FMR in symptomatic heart failure subjects. This single arm registry will provide valuable new information regarding use of the MitraClip® NT System under more "real world" conditions. COAPT study completed recruiting subjects in June 2017. COAPT CAS completed recruiting subjects in March 2019. A total of 162 subjects were enrolled in the COAPT CAS Group.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Symptomatic functional MR (≥3+) due to cardiomyopathy of either ischemic or non-ischemic etiology determined by assessment of a qualifying transthoracic echocardiogram (TTE) obtained within 90 days and transesophageal echocardiogram (TEE) obtained within 180 days prior to subject registration, with MR severity based principally on the TTE study, confirmed by the Echocardiography Core Lab (ECL). The ECL may request a transesophageal echocardiogram (TEE) to confirm MR etiology.
- •Note: Functional MR requires the presence of global or regional left ventricular wall motion abnormalities, which are believed to be the primary cause of the MR. If a flail leaflet or other evidence of degenerative MR is present, the subject is not eligible even if global or regional left ventricular systolic dysfunction is present.
- •Note: Qualifying TTE must be obtained after the subject has been stabilized on optimal therapy including Guideline Directed Medical Therapy (GDMT) and at least 30 days after:
- •a greater than 100% increase or greater than 50% decrease in dose of GDMT
- •revascularization and/or implant of Cardiac Resynchronization Therapy device (CRT or CRT-D) or reprogramming of an implanted CRT or CRT-D that results in increased biventricular pacing (from \<92% to ≥92%)
- •In the judgment of the HF specialist investigator at the site, the subject has been adequately treated per applicable standards, including for coronary artery disease, left ventricular dysfunction, mitral regurgitation and heart failure (e.g., with cardiac resynchronization therapy, revascularization, and/or GDMT). The Eligibility Committee must also concur that the subject has been adequately treated.
- •New York Heart Association (NYHA) Functional Class II, III or ambulatory IV.
- •The Local Site Heart Team (CT surgeon and HF specialist investigators) and the Central Eligibility Committee concur that surgery will not be offered as a treatment option and that medical therapy is the intended therapy for the subject, even if the subject is randomized to the Control group.
- •The subject has had at least one hospitalization for heart failure in the 12 months prior to subject registration and/or a corrected brain natriuretic peptide (BNP) ≥300 pg/ml or corrected n-Terminal pro- brain natriuretic peptide NT-proBNP ≥1500 pg/ml measured within 90 days prior to subject registration ("corrected" refers to a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m2 in BMI above a reference BMI of 20 kg/m2).
- •Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on GDMT and at least 30 days after:
Exclusion Criteria
- •Chronic Obstructive Pulmonary Disease (COPD) requiring continuous home oxygen therapy or chronic outpatient oral steroid use.
- •Untreated clinically significant coronary artery disease requiring revascularization.
- •Coronary artery bypass grafting (CABG) within 30 days prior to subject registration.
- •Percutaneous coronary intervention within 30 days prior to subject registration.
- •Transcatheter aortic valve replacement (TAVR) within 30 days prior to subject registration.
- •Tricuspid valve disease requiring surgery or transcatheter intervention.
- •Aortic valve disease requiring surgery.
- •Cerebrovascular accident within 30 days prior to subject registration.
- •Severe symptomatic carotid stenosis (\> 70% by ultrasound).
- •Carotid surgery or stenting within 30 days prior to subject registration.
Outcomes
Primary Outcomes
Primary Safety Endpoint - Percentage of Participants With Freedom From Device Related Complications at 12 Months
Time Frame: 12 months
Percentage of Participants with Freedom from Device related Complications at 12 Months. Composite of Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, and any device related complications requiring non-elective cardiovascular surgery.
Primary Effectiveness Endpoint
Time Frame: 24 months
Recurrent HF hospitalizations (HFH) through 24 months, analyzed when the last subject completes 12-month follow-up
Secondary Outcomes
- Major Vascular Complications (COAPT CAS Study Analysis)(30 days)
- New York Heart Association (NYHA) Functional Class (COAPT CAS Study Analysis)(30 days)
- Number of Deaths at 12 Months (All Cause Mortality)(12 months)
- Quality of Life (QOL) (COAPT CAS Study Analysis) Quality of Life (QoL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)(30 days)
- Death and Primary Cause of Death (COAPT CAS Study Analysis)(5 years)
- Six Minute Walk Test (6MWT Distance or 6MWD) (COAPT CAS Study Analysis)(30 days)
- Renal Complication With Requirement for Dialysis (COAPT CAS Study Analysis)(30 days)
- Transient Ischemic Attack (TIA) (COAPT CAS Study Analysis)(30 days)
- Change in Left Ventricular End Diastolic Volume (LVEDV)(12 months over baseline)
- Major and/or Life Threatening Bleeding (COAPT CAS Study Analysis)(30 days)
- Number of Participants With Mitral Regurgitation Severity Grade of 2+ or Lower at 12 Months(12 months)
- Stroke (COAPT CAS Study Analysis)(5 years)
- Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis)(5 years)
- Mitral Regurgitation (MR) Severity (COAPT CAS Study Analysis)(30 days)
- Change in Quality of Life (QoL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)(12 months over baseline)
- Myocardial Infarction (MI) (COAPT CAS Study Analysis)(5 years)
- Percentage of Patients Free From the Composite of All-cause Death, Stroke, MI, or Non-elective Cardiovascular Surgery for Device Related Complications in the Device Group(30 days post-procedure in the Device group)
- Change in Distance Walked on the 6 Minute Walk Test (6MWT Distance or 6MWD)(12 months over baseline)
- Kaplan-Meier Freedom From All-cause Mortality(24 months)
- Number of Participants With New York Heart Association (NYHA) Functional Class I/II(12 months)
- Recurrent Hospitalizations - All Cause(24 Months)
- Death or HF Hospitalization Within 24 Months (Finkelstein-Schoenfeld Analysis of All-Cause Death or Recurrent HF Hospitalization Through 24 Months)(24 months)