Mitral Valve Regurgitation
Conditions
Keywords
surgical mitral valve repair, transcatheter edge-to-edge repair
Brief summary
This is a prospective, multicenter, open-label, randomized trial comparing mitral valve (MV) transcatheter edge-to-edge repair (TEER) to surgical repair (1:1 ratio) in patients with primary, degenerative mitral regurgitation (MR). The trial will be conducted in the U.S., Canada, Germany, Spain, and the United Kingdom, and is designed as a strategy trial. Thus, all devices legally marketed for TEER of primary degenerative MR in a particular country are eligible to be used in this trial.
Detailed description
The primary aim of this study is to evaluate the long-term effectiveness and safety of MV TEER compared with surgical repair in patients with primary, degenerative MR. The secondary aim is to analyze the relationship between the adequacy of MR correction at one-year post intervention and longer-term clinical outcomes (death, heart failure hospitalizations/urgent care visits, valve re-interventions, and quality of life). The tertiary aim of this trial is to evaluate a range of patient-centered outcomes (quality of life, functional status, and discharge location) of transcatheter edge-to-edge MV repair compared with MV surgical repair in patients with primary, degenerative mitral regurgitation. This study is closely integrated with the PRIMARY Ancillary Substudy (NCT07103733) The patient population for this trial consists of adult patients with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible. Because the use of the commercial edge-to-edge mitral repair device in the U.S. is approved only in patients considered to be at prohibitive risk of MV surgery by a heart team, use of such devices in this trial is considered investigational by the FDA. As such, this trial will be conducted under an Investigational Device Exemption (IDE). Outcomes will be measured from randomization over a period of 5 years post intervention. The estimated enrollment period is 36 months, and all patients will be followed from randomization for up to 10 years post intervention for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.
Interventions
PROCEDUREMitral valve repair
Patients who are randomized to the surgical arm will undergo mitral surgery. Mitral surgery will be conducted using general anesthesia and cardiopulmonary bypass. Mitral surgery may be performed via a sternotomy or a right thoracotomy approach with or without robotic assistance. Standard techniques commonly include a ring or band annuloplasty to correct and prevent annular dilatation; leaflet prolapse and redundancy may be corrected by leaflet resection techniques and / or chordal reconstruction.
Patients will be treated with a commercially-approved edge-to-edge mitral repair device. The steerable guide catheter (guide) is inserted into the femoral vein and advanced across the inter-atrial septum using image guided puncture. Fluoroscopic and echocardiographic guidance will be used to visualize the devices and assess the repair. The guide is positioned over the MV and the clip/clasp delivery system is inserted into the guide and positioned over the MV in accordance with the manufacturer's instructions. The delivery catheter is advanced until the clip/clasp emerges from the tip of the guide into the left atrium. The catheter is manipulated using the control handle until the clip/clasp is correctly oriented with respect to the line of coaptation of the mitral valve. The clip/clasp is opened, and advanced across the mitral valve into the left ventricle then pulled back to grasp the leaflets.
Sponsors
Annetine Gelijns
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible and consented patients will be randomized 1:1 to a TEER versus surgical repair. Patient randomization will be stratified by clinical site and by surgical risk profile, namely low, intermediate, and high surgical risk. Primary effectiveness will be analyzed by intention-to-treat; that is, the patients will be grouped by their assignment at randomization whether or not they actually received the treatment to which they were assigned.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The patient population for this trial consists of adults with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible. Specific inclusion and
Exclusion criteria
are listed below. All patients who meet eligibility criteria will be included in the study regardless of gender, race, or ethnicity. Inclusion Criteria: * Adult patients ≥60 years with moderately-severe or severe (3+ or 4+/4+) primary degenerative (Carpentier type II) MR defined by transthoracic echocardiography * Clinical indication for MV intervention and anatomic candidate for both surgical MV repair and transcatheter edge-to-edge repair (TEER) per local heart team assessment with central eligibility committee verification * Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on local heart team assessment and central eligibility committee verification (see ACC/AHA 2020 guidelines for the management of patients with valvular heart disease) * Patients with AF who meet an indication for a concomitant ablation procedure be included provided the local heart team and central eligibility committee decide they are eligible for both catheter-based and surgical ablation. * Ability to perform 6-minute walk test (6MWT) and complete Kansas City Cardiomyopathy Questionnaire (KCCQ) instrument
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score. | 3 years post intervention | All-cause mortality, valve re-intervention, hospitalizations/urgent visits for heart failure (without a blanking period), or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum of 3 years post intervention. Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adequacy of MR correction | one year post intervention | Adequacy of MR correction at one year post intervention, defined as \< 2+ MR as assessed by TTE |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | up to 10 years post intervention | Disease-specific quality of life as measured by the KCCQ at 6-month time intervals up to 5 years. KCCQ has 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy. The symptom frequency and symptom burden domains are merged into a total symptom score, which can be combined with the physical limitation domain to create a clinical summary score. All scores are scaled 0 to 100, with higher scores indicating better health outcome. |
| Procedure failure | End of procedure | Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure. |
| All-cause mortality | 5 years post randomization | All-cause mortality through 5 years post randomization |
| Cardiovascular and non-cardiovascular mortality | 5 years post intervention | Cardiovascular and non-cardiovascular mortality from randomization through 5 years post intervention |
| Valve re-interventions | 5 years post intervention | Valve re-interventions through 5 years post intervention |
| Serious or protocol-defined adverse events | 5 years post intervention | Serious or protocol-defined adverse events, including stroke, acute kidney injury (AKI), and renal failure, through 5 years |
| MR grade | up to 6 years post intervention | Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.) |
| Left Ventricular Ejection Fraction (LVEF) | up to 6 years post intervention | Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. |
| Left Ventricular End Diastolic Dimension (LVEDD) | up to 6 years post intervention | Left ventricular end diastolic dimension (LVEDD) is the diameter across the left ventricle of the heart at the end of diastole, that is, when the heart muscle is maximally relaxed, and usually corresponds to its largest diameter. |
| Left Ventricular End Systolic Dimension (LVESD) | up to 6 years post intervention | Left ventricular end systolic dimension (LVESD) is the diameter across the left ventricle of the heart at the end of systole, that is, when the heart muscle is maximally contracted, and usually corresponds to its smallest diameter. |
| Left Ventricular End Diastolic Volume (LVEDV) | up to 6 years post intervention | Left Ventricular end diastolic volume (LVEDV) is the volume of blood in the left ventricle at the end of the diastole or ventricular filling. |
| Left Ventricular End Systolic Volume (LVESV) | up to 6 years post intervention | Left Ventricular end systolic volume (LVESV) is the volume of blood in the left ventricle at the end of the systolic ejection phase immediately before the beginning of diastole or ventricular filling. |
| Mitral valve gradient | up to 6 years post intervention | The valve gradient is the difference in pressure on each side of the valve. When a valve is narrowed (a condition called stenosis), the pressure on the front of the valve builds up as blood is forced through the narrow opening. This causes a larger pressure difference between the front and back of the valve. The valve gradient can be used to determine the severity of the valve disorder. |
| Forward stroke volume | up to 6 years post intervention | The forward stroke volume is the volume entering the aorta. |
| 6 Minute Walk Test (6MWT) | up to 5 years post intervention | Functional status as measured by the 6MWT at yearly time intervals over 5 years. 6MT - The distance covered over a time of 6 minutes |
| EuroQol- 5 Dimension (EQ-5D) | through 10 years post intervention | Generic QoL as measured by the EuroQol-5D (EQ-5D). The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ- 5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status). |
| Length of stay (LOS) | through 10 years post intervention | Length of stay as measured by number of days hospitalized. |
| ICU days of index hospitalization | through 10 years post intervention | Number of ICU days of index hospitalization |
| Number and reasons for readmissions | through 10 years post intervention | Number and reasons for readmissions, including for valve re-intervention and readmissions/urgent visits for heart failure |
| Cost | through 10 years post intervention | Costs associated with the index hospitalization as well as follow-up readmissions will be measured. |
| Cost-effectiveness | through 10 years post intervention | A cost-effectiveness analysis (CEA) comparing cumulative costs and quality-adjusted life years (QALYs) of transcatheter edge-to-edge repair vs surgical repair will be performed from U.S., Canadian, German and United Kingdom health care sector perspectives according to national guidelines. |
| Number of participants with stroke with disability | 30 days post-intervention | Stroke with disability is defined as a modified Rankin score of ≥ 2 and/or major bleeding (BARC Type 3b, 3c and 5) by 30 days post-intervention |
Countries
Canada, Germany, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJoanna Chikwe, MD
Cedars Sinai
STUDY_DIRECTORMartin Leon, MD
Columbia University
STUDY_DIRECTORPatrick O'Gara, MD
Brigham and Women's Hospital
Outcome results
None listed