Mitral Implantation of TRAnscatheter vaLves
- Conditions
- Mitral Valve Disease
- Interventions
- Device: Transcatheter Mitral Valve Replacement
- Registration Number
- NCT02370511
- Lead Sponsor
- Mayra Guerrero
- Brief Summary
The purpose of this trial is to establish the safety and feasibility of the Edwards SAPIEN XT™and SAPIEN 3™ device and delivery systems in patients with severe symptomatic calcific mitral valve disease with severe mitral annular calcification who are not candidates for standard mitral valve surgery.
- Detailed Description
Design:
A prospective pilot study enrolling extremely high surgical risk patients with symptomatic severe calcific mitral valve disease undergoing implantation of an Edwards Sapien XT or SAPIEN 3 valve in the mitral position.
There are three arms in this study evaluating three separate patient populations described below:
* Native Mitral Valve with severe Mitral Annular Calcification (MAC): Patients with symptomatic severe disease of a native mitral valve due to severe mitral annular calcification.
* Valve-in-Ring: Patients with symptomatic failing surgical rings resulting in severe mitral regurgitation or stenosis.
* Valve-in-Valve: Patients with failing bioprosthetic surgical valves with severe regurgitation or stenosis
The delivery approaches include: standard transeptal, modified transeptal approach with a guidewire externalized through a sheath percutaneously placed in the left ventricle, surgical trasnapical and surgical transatrial delivery approach with or without surgical resection of the anterior mitral valve (MV) leaflet (in the native mitral valve arm).
The MITRAL Trial site investigative team (heart team) consists of dedicated representatives from cardiac surgery, interventional cardiology, echocardiology, neurology, study coordination and other multi-disciplinary team members consistent with a transcatheter aortic valve replacement (TAVR) model.
Endpoints
Most endpoints were defined following the Mitral Valve Academic Research Consortium (MVARC) recommendations with minor modifications.73
The primary safety endpoint is: technical success at exit from the cath lab
• Technical success (at exit from the cath lab) is defined as:
* Successful vascular and/or TA access, delivery and retrieval of the transcatheter valve delivery system
* Deployment of a single valve
* Correct position of transcatheter valve in the mitral annulus
* Adequate performance of the prosthetic heart valve (mean mitral valve gradient (MVG) \<10 mmHg) without residual mitral regurgitation (MR) grade ≥2 (+)
* No need for additional surgery or re-intervention (includes drainage of pericardial effusion)
* The patient leaves the cath lab alive
The primary performance endpoint is: absence of MR grade 2 (+) or greater or mean MVG ≥10 mmHg at 30 days and 1 year.
Secondary safety endpoints include: Procedural success and all -cause mortality at 30 days and 1 year.
* Procedural Success (30 days) in defined as:
* Device success at 30 days
* No device/procedure related severe adverse event (SAE's) including: death, stroke, MI or coronary ischemia requiring PCI or CABG, stage 2 or 3 AKI including dialysis, life threatening bleeding, major vascular or access complications (arterial, venous, or TA - any event requiring additional unplanned surgical or transcatheter intervention), pericardial effusion or tamponade requiring drainage, severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical treatments such as ultrafiltration or hemodynamic assist devices including intra-aortic balloon pump or left ventricular assist device, or prolonged intubation for ≥48 hrs, or any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention.
* Device success is defined as:
* Stroke free survival with original valve in place
* No need for additional surgery or re-intervention related to the procedure, access or to the replacement valve
* Proper placement and intended function of the replacement valve, including
* No migration, fracture, thrombosis, hemolysis or endocarditis
* No replacement valve stenosis (MV gradient \< 10 mmHg)
* Replacement valve regurgitation \< 2 + (including central and paravalvular leak) and without associated hemolysis
* No increase in AI from baseline (more than 1 grade) and LVOT gradient \< 20 mmHg increase from baseline
Additional secondary safety and effectiveness endpoints will be evaluated at two time points: (1) acute, covering events occurring out to 30 days or hospital discharge, whichever is longer; and (2) longer-term, covering events from 31 days to 1 year, and include the following:
Additional Safety Endpoints:
Freedom from
* all stroke and TIA (MVARC)
* myocardial infarction
* major vascular complication (MVARC)
* life-threatening bleeding (MVARC)
* mitral valve reoperation or catheter-based intervention for: valve thrombosis, valve displacement, or other valve placed procedure-related complication
* hemolysis
* endocarditis
* moderate or severe central mitral insufficiency ≥ 2 (+), and/or moderate or severe perivalvular leak causing ≥ 2 (+) mitral insufficiency
* significant mitral stenosis (mean MVG \>10 mmHg)
* new permanent pacemaker insertion
* new aortic valve dysfunction (difference greater than 1(+) severity compared with baseline)
* new LVOT gradient ≥ 20 mmHg, or ≥ 20 mmHg increase from baseline LVOT gradient.
* acute kidney injury (MVARC)
* new onset atrial fibrillation
* blood transfusion
* access site infection
* need for iatrogenic ASD closure after index procedure
Additional Effectiveness Endpoints:
1. Rehospitalization at 1 year and Total days alive and out of hospital (from date of index procedure)
2. Clinical improvement per NYHA Class (from baseline) by at least 1 class.
3. Clinical improvement per Quality of Life instruments (\>10 points from baseline): (KCCQ 12) (Appendix N)
4. Clinical improvement per 6 Minute Walk Test (\> 50 meters from baseline) and 5 meter walk test. (Appendix H)
5. Mean ICU and total index procedure hospital length of stay
Additional Valve Performance Endpoints:
1. Freedom from major mitral paravalvular leak
2. Improvement in hemodynamic function: mean gradient
3. Freedom from structural valve deterioration
4. Total mitral regurgitation
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 91
Not provided
Candidates will be excluded from the study if any of the following conditions are present:
-
Heart Team assessment of operability (the heart team considers the patient is a surgical candidate).
-
Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)].
-
Mitral annulus is not calcified (only applies to patients included in Native MV arm).
-
Complex untreated coronary artery disease:
- Unprotected left main coronary artery
- Syntax score > 32 (in the absence of prior revascularization)
-
Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker is not excluded.
-
Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless BMV is a bridge to procedure after a qualifying ECHO).
-
Patients with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation.
-
Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt < 50,000 cell/mL).
-
Hypertrophic obstructive cardiomyopathy (HOCM).
-
Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation.
-
Need for emergency surgery for any reason.
-
Severe ventricular dysfunction with LVEF < 20%.
-
Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
-
Active upper GI bleeding within 3 months (90 days) prior to procedure.
-
A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
-
For patients enrolled in the Native MV arm: Native mitral annulus size < 275 mm2 or > 740 mm2 as measured by CT scan.
For patients in Valve-in-Ring arm: surgical ring with a true mean internal diameter ≤18 mm or ≥ 29 mm or an area < 275 mm2 or > 740 mm2 as measured by CT scan. Caution recommended in:
- Incomplete bands due to risk of paravalvular leak and risk of LVOT obstruction. Careful measurements by CT and CT-guided procedural planning is recommended.
- Non-circular rigid or semi-flexible rings (e.g., D-shaped, saddle shaped, etc) due to risk of para-valvular leak and/or out of round or incomplete valve expansion.
For patients in Valve-in-Valve arm: surgical bioprosthesis with a true internal diameter ≤18 mm or ≥ 29 mm
-
Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure.
-
Estimated life expectancy < 24 months (730 days) due to carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
-
Expectation that patient will not improve despite treatment of mitral stenosis
-
Active bacterial endocarditis within 6 months (180 days) of procedure.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Valve-in-Valve Transcatheter Mitral Valve Replacement Patients with symptomatic failing surgical bioprostheses resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (Valve-in-valve). Valve-in-Ring Transcatheter Mitral Valve Replacement Patients with symptomatic failing surgical rings resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (valve-in-ring). Native mitral valve with severe MAC Transcatheter Mitral Valve Replacement Patients with symptomatic severe calcific native mitral valve disease with severe mitral annular calcification who have extremely high surgical risk for standard surgical mitral valve replacement, will undergo transcatheter mitral valve replacement.
- Primary Outcome Measures
Name Time Method Mitral Valve Gradient (MVG) 30 days and 1 year MVG assessed by echocardiography measured in mmHg
Absence of MR Grade 2 (+) or Greater 30 days and 1 year Number of subjects to have absence of MR grade 2 (+) or greater assessed with echocardiography. MR severity grading system ranging from Grade 1=mild; Grade 4=severe.
Technical Success at Exit From the Cath Lab. 30 days Number of subject to achieve technical success (at exit from cath lab) is defined as:
* Successful vascular delivery and retrieval of transcatheter valve delivery system
* Deployment of single valve
* Correct position of transcatheter valve
* Adequate performance of prosthesis (MVA \> 1.5 cm2) without residual MR grade ≥2 (+)
* No need for additional surgery or re-intervention
* Patient leaves cath lab alive
- Secondary Outcome Measures
Name Time Method Procedural Success 30 days Number of subject to have procedural success as defined as no device/procedure related SAE's including: death, stroke, MI or coronary ischemia requiring PCI or CABG, stage 2 or 3 AKI including dialysis, life threatening bleeding, major vascular or access complications (arterial, venous, or TA - any event requiring additional unplanned surgical or transcatheter intervention), pericardial effusion or tamponade requiring drainage, severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical treatments such as ultrafiltration or hemodynamic assist devices including intra-aortic balloon pump or left ventricular assist device, or prolonged intubation for ≥48 hrs, or any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention.
Trial Locations
- Locations (15)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Evanston Hospital / North Shore University HealthSystem
🇺🇸Evanston, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Banner University Medical Center
🇺🇸Phoenix, Arizona, United States
Piedmont HealtCare
🇺🇸Atlanta, Georgia, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
MedStar Washington Medical Center
🇺🇸Washington, District of Columbia, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States