NCT02370511

Mitral Implantation of TRAnscatheter vaLves

The Safety and Feasibility of the SAPIEN XTTM Transcatheter Heart Valve With NovaFlex and Ascendra Delivery Systems and SAPIEN 3 With Commander Delivery System in Patients With Symptomatic Severe Calcific Mitral Valve Disease With Severe Mitral Annular Calcification and Patients With Failing Mitral Surgical Rings or Bioprostheses Who Are Not Candidates for Mitral Valve Surgery.

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 91 (actual)
• Sponsor: Mayra Guerrero · Academic / Other
• Sex: All
• Age: 22 Years
• Healthy volunteers: Not accepted

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

Conditions

• Mitral Valve Disease

Interventions

Type	Name	Description
DEVICE	Transcatheter Mitral Valve Replacement	Implantation of a balloon expandable Edwards SAPIEN XT or SAPIEN 3 transcatheter heart valve in the mitral position.

Timeline

• Start date: 2015-02-25
• Primary completion: 2018-12-01
• Completion: 2018-12-01
• First posted: 2015-02-25
• Last updated: 2023-10-10
• Results posted: 2021-08-16

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated device study