Mitral Valve DiseaseMITRALNCT02370511
Mitral Implantation of TRAnscatheter vaLves
A study testing Transcatheter Mitral Valve Replacement in people with Mitral Valve Disease, run by Mayra Guerrero at 15 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Mitral Valve Disease
- What is being tested?
- Transcatheter Mitral Valve Replacement
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 15 sitesUnited States
- Study dates
- 25 Feb 2015to Dec 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Candidates must meet the following criteria:
- Patient has severe calcific native mitral valve stenosis with mitral annular calcification with echocardiographically derived mitral valve area (MVA) of ≤1.5 cm2, or severe mitral regurgitation with severe mitral annular calcification and at least moderate mitral valve stenosis. Qualifying echo must be within 60 days of the date of the procedure.
- Patient is symptomatic from mitral valve disease, as demonstrated by reported NYHA Functional Class II or greater, or symptoms during stress test.
- The patient is at least 22 years old.
- The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.
- The heart team agrees that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the STS score is ≥15% or the probability of death or serious, irreversible morbidity is ≥ 50%. The surgeons' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the STS score to additionally identify the risks in the patient (some medical factors and definitions are provided below). At least one of the cardiac surgeon assessors must have physically evaluated the patient. All patients must be approved by the Patient Selection and Procedure Management Steering Committee (at least 2 member votes, one must be a cardiac surgeon).
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- The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
- The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up.
- All Candidates must meet the following criteria:
- Patient has a failing surgical ring in the mitral position with severe mitral regurgitation or stenosis (echocardiographically derived mitral valve area [MVA] of ≤1.5 cm2. Qualifying echo must be within 60 days of the date of the procedure.
- Patient is symptomatic from mitral valve disease, as demonstrated by reported NYHA Functional Class II or greater, or symptoms during stress test, or severe hemolytic anemia requiring blood transfusions and no other cause of hemolytic anemia is found after extensive work up.
- Inclusion Criteria items #3 to 7 will be the same as in Native MV arm described above
- All Candidates must meet the following criteria:
- Patient has a failing surgical bioprosthesis in the mitral position with severe mitral regurgitation or stenosis with echocardiographically derived mitral valve area (MVA) of ≤1.5 cm2. Qualifying echo must be within 60 days of the date of the procedure.
- Patient is symptomatic from mitral valve disease, as demonstrated by reported NYHA Functional Class II or greater, or symptoms during stress test.
- Inclusion Criteria items #3 to 7 will be the same as in Native MV arm described above
Who cannot join
- 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
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- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Piedmont HealtCare
Atlanta, Georgia, 30309
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Henry Ford Hospital
Detroit, Michigan, 48202
Evanston Hospital / North Shore University HealthSystem
Evanston, Illinois, 60201
Memorial Hermann Texas Medical Center
Houston, Texas, 77030
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Intermountain Medical Center
Murray, Utah, 48107
Mount Sinai Hospital
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Banner University Medical Center
Phoenix, Arizona, 85006
Mayo Clinic
Rochester, Minnesota, 55905
University of Washington Medical Center
Seattle, Washington, 98195
MedStar Washington Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: 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.
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.
Read the 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:
- Rehospitalization at 1 year and Total days alive and out of hospital (from date of index procedure)
- Clinical improvement per NYHA Class (from baseline) by at least 1 class.
- Clinical improvement per Quality of Life instruments (>10 points from baseline): (KCCQ 12) (Appendix N)
- Clinical improvement per 6 Minute Walk Test (> 50 meters from baseline) and 5 meter walk test. (Appendix H)
- Mean ICU and total index procedure hospital length of stay
Additional Valve Performance Endpoints:
- Freedom from major mitral paravalvular leak
- Improvement in hemodynamic function: mean gradient
- Freedom from structural valve deterioration
- Total mitral regurgitation
- Conditions
- Mitral Valve Disease
- Being tested
- Transcatheter Mitral Valve Replacement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcatheter Mitral Valve ReplacementDevice
Implantation of a balloon expandable Edwards SAPIEN XT or SAPIEN 3 transcatheter heart valve in the mitral position.
| Study group | Role | What they receive |
|---|---|---|
| Native mitral valve with severe MAC | Experimental | 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. Receives: Device: Transcatheter Mitral Valve Replacement |
| Valve-in-Ring | Experimental | Patients with symptomatic failing surgical rings resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (valve-in-ring). Receives: Device: Transcatheter Mitral Valve Replacement |
| Valve-in-Valve | Experimental | Patients with symptomatic failing surgical bioprostheses resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (Valve-in-valve). Receives: Device: Transcatheter Mitral Valve Replacement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Technical Success at Exit From the Cath Lab.
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
Measured: 30 days
Absence of MR Grade 2 (+) or Greater
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.
Measured: 30 days and 1 year
Mitral Valve Gradient (MVG)
MVG assessed by echocardiography measured in mmHg
Measured: 30 days and 1 year
Secondary outcomes (1)
Procedural Success
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.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study start25 Feb 2015
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Mitral Valve DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayra Guerrero
- Sponsor type
- University, hospital or other
- Collaborators
- Henry Ford Hospital
- Responsible party
- Sponsor-investigator, Mayra Guerrero, Mayo Clinic
- Investigators
- Mayra E. Guerrero, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370511
- Sponsor's protocol ID
- 18-006601
- Acronym
- MITRAL
- Status last verified
- Oct 2023
- First submitted
- 18 Feb 2015
- Last updated
- 10 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Guerrero M, Greenbaum A, O'Neill W. First in human percutaneous implantation of a balloon expandable transcatheter heart valve in a severely stenosed native mitral valve. Catheter Cardiovasc Interv. 2014 Jun 1;83(7):E287-91. doi: 10.1002/ccd.25441. Epub 2014 Mar 14.
PubMed 24532349Sinning JM, Mellert F, Schiller W, Welz A, Nickenig G, Hammerstingl C. Transcatheter mitral valve replacement using a balloon-expandable prosthesis in a patient with calcified native mitral valve stenosis. Eur Heart J. 2013 Sep;34(33):2609. doi: 10.1093/eurheartj/eht254. Epub 2013 Jul 4. No abstract available.
PubMed 23828829Hasan R, Mahadevan VS, Schneider H, Clarke B. First in human transapical implantation of an inverted transcatheter aortic valve prosthesis to treat native mitral valve stenosis. Circulation. 2013 Aug 6;128(6):e74-6. doi: 10.1161/CIRCULATIONAHA.113.001466. No abstract available.
PubMed 23918190Fassa AA, Himbert D, Brochet E, Depoix JP, Cheong AP, Alkhoder S, Nataf P, Vahanian A. Transseptal transcatheter mitral valve implantation for severely calcified mitral stenosis. JACC Cardiovasc Interv. 2014 Jun;7(6):696-7. doi: 10.1016/j.jcin.2013.12.204. Epub 2014 May 14. No abstract available.
PubMed 24835326Ribeiro HB, Doyle D, Urena M, Allende R, Amat-Santos I, Pasian S, Bilodeau S, Mohammadi S, Paradis JM, DeLarochelliere R, Rodes-Cabau J, Dumont E. Transapical mitral implantation of a balloon-expandable valve in native mitral valve stenosis in a patient with previous transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2014 Oct;7(10):e137-9. doi: 10.1016/j.jcin.2014.02.024. Epub 2014 Sep 17. No abstract available.
PubMed 25240553Ferrari E, Niclauss L, Locca D, Marcucci C. On-pump fibrillating heart mitral valve replacement with the SAPIEN XT transcatheter heart valve. Eur J Cardiothorac Surg. 2014 Apr;45(4):749-51. doi: 10.1093/ejcts/ezt364. Epub 2013 Jul 11.
PubMed 23847181Himbert D, Bouleti C, Iung B, Nejjari M, Brochet E, Depoix JP, Ghodbane W, Fassa AA, Nataf P, Vahanian A. Transcatheter valve replacement in patients with severe mitral valve disease and annular calcification. J Am Coll Cardiol. 2014 Dec 16;64(23):2557-8. doi: 10.1016/j.jacc.2014.09.047. No abstract available.
PubMed 25500243Guerrero M, Wang DD, Eleid MF, Pursnani A, Salinger M, Russell HM, Kodali SK, George I, Bapat VN, Dangas GD, Tang GHL, Inglesis I, Meduri CU, Palacios I, Reisman M, Whisenant BK, Jermihov A, Kaptzan T, Lewis BR, Tommaso C, Krause P, Thaden J, Oh JK, Douglas PS, Hahn RT, Leon MB, Rihal CS, Feldman T, O'Neill WW. Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):830-845. doi: 10.1016/j.jcin.2021.01.052.
PubMed 33888229Guerrero M, Wang DD, Pursnani A, Salinger M, Russell HM, Eleid M, Chakravarty T, Ng MH, Kodali SK, Meduri CU, Pershad A, Satler L, Waksman R, Palacios I, Smalling R, Reisman M, Gegenhuber M, Kaptzan T, Lewis B, Tommaso C, Krause P, Thaden J, Oh J, Douglas PS, Hahn RT, Kar S, Makkar R, Leon MB, Feldman T, Rihal C, O'Neill WW. Prospective Evaluation of TMVR for Failed Surgical Annuloplasty Rings: MITRAL Trial Valve-in-Ring Arm 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):846-858. doi: 10.1016/j.jcin.2021.01.051.
PubMed 33888230Guerrero M, Pursnani A, Narang A, Salinger M, Wang DD, Eleid M, Kodali SK, George I, Satler L, Waksman R, Meduri CU, Rajagopal V, Inglessis I, Palacios I, Reisman M, Eng MH, Russell HM, Pershad A, Fang K, Kar S, Makkar R, Saucedo J, Pearson P, Bokhary U, Kaptzan T, Lewis B, Tommaso C, Krause P, Thaden J, Oh J, Lang RM, Hahn RT, Leon MB, O'Neill WW, Feldman T, Rihal C. Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):859-872. doi: 10.1016/j.jcin.2021.02.027.
PubMed 33888231Guerrero ME, Eleid MF, Wang DD, Pursnani A, Kodali SK, George I, Palacios I, Russell H, Makkar RR, Kar S, Satler LF, Rajagopal V, Dangas G, Tang GHL, McCabe JM, Whisenant BK, Fang K, Balan P, Smalling R, Kaptzan T, Lewis B, Douglas PS, Hahn RT, Thaden J, Oh JK, Leon M, O'Neill W, Rihal C. 5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results. JACC Cardiovasc Interv. 2023 Sep 25;16(18):2211-2227. doi: 10.1016/j.jcin.2023.06.041.
PubMed 37758379Sticchi A, Reineke D, Praz F, Windecker S. Transcatheter Mitral Valve Replacement for Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Using Balloon-Expandable Transcatheter Heart Valves. JACC Cardiovasc Interv. 2021 Apr 26;14(8):873-878. doi: 10.1016/j.jcin.2021.02.034. No abstract available.
PubMed 33888232
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT02370511
- Acronym / sponsor ID
- MITRAL / 18-006601
- Conditions
- Mitral Valve Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Mayra GuerreroUniversity, hospital or other
- Collaborators
- Henry Ford Hospital
- Study start
- 25 Feb 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 16 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Rehospitalization at 1 year and Total days alive and out of hospital (from date of index procedure)
- Clinical improvement per NYHA Class (from baseline) by at least 1 class.
- Clinical improvement per Quality of Life instruments (>10 points from baseline): (KCCQ 12) (Appendix N)
- Clinical improvement per 6 Minute Walk Test (> 50 meters from baseline) and 5 meter walk test. (Appendix H)
- Mean ICU and total index procedure hospital length of stay
Additional Valve Performance Endpoints:
- Freedom from major mitral paravalvular leak
- Improvement in hemodynamic function: mean gradient
- Freedom from structural valve deterioration
- Total mitral regurgitation
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Native mitral valve with severe MAC | Experimental | Device: Transcatheter Mitral Valve ReplacementPatients 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. |
| Valve-in-Ring | Experimental | Device: Transcatheter Mitral Valve ReplacementPatients with symptomatic failing surgical rings resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (valve-in-ring). |
| Valve-in-Valve | Experimental | Device: Transcatheter Mitral Valve ReplacementPatients with symptomatic failing surgical bioprostheses resulting in severe mitral regurgitation or stenosis will undergo transcatheter mitral valve replacement (Valve-in-valve). |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patient has severe calcific native mitral valve stenosis with mitral annular calcification with echocardiographically derived mitral valve area (MVA) of ≤1.5 cm2, or severe mitral regurgitation with severe mitral annular calcification and at least moderate mitral valve stenosis. Qualifying echo must be within 60 days of the date of the procedure.
- Patient is symptomatic from mitral valve disease, as demonstrated by reported NYHA Functional Class II or greater, or symptoms during stress test.
- The patient is at least 22 years old.
- The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.
- The heart team agrees that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the STS score is ≥15% or the probability of death or serious, irreversible morbidity is ≥ 50%. The surgeons' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the STS score to additionally identify the risks in the patient (some medical factors and definitions are provided below). At least one of the cardiac surgeon assessors must have physically evaluated the patient. All patients must be approved by the Patient Selection and Procedure Management Steering Committee (at least 2 member votes, one must be a cardiac surgeon).
Key exclusion criteria (27 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcatheter Mitral Valve ReplacementImplantation of a balloon expandable Edwards SAPIEN XT or SAPIEN 3 transcatheter heart valve in the mitral position. | Device | Native mitral valve with severe MAC, Valve-in-Ring, Valve-in-Valve |
Primary outcome
Technical Success at Exit From the Cath Lab.
Time frame: 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
Absence of MR Grade 2 (+) or Greater
Time frame: 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.
Mitral Valve Gradient (MVG)
Time frame: 30 days and 1 year
MVG assessed by echocardiography measured in mmHg
1 secondary outcome
Procedural Success
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24532349Guerrero M, Greenbaum A, O'Neill W. First in human percutaneous implantation of a balloon expandable transcatheter heart valve in a severely stenosed native mitral valve. Catheter Cardiovasc Interv. 2014 Jun 1;83(7):E287-91. doi: 10.1002/ccd.25441. Epub 2014 Mar 14.
- Background: PubMed 23828829Sinning JM, Mellert F, Schiller W, Welz A, Nickenig G, Hammerstingl C. Transcatheter mitral valve replacement using a balloon-expandable prosthesis in a patient with calcified native mitral valve stenosis. Eur Heart J. 2013 Sep;34(33):2609. doi: 10.1093/eurheartj/eht254. Epub 2013 Jul 4. No abstract available.
- Background: PubMed 23918190Hasan R, Mahadevan VS, Schneider H, Clarke B. First in human transapical implantation of an inverted transcatheter aortic valve prosthesis to treat native mitral valve stenosis. Circulation. 2013 Aug 6;128(6):e74-6. doi: 10.1161/CIRCULATIONAHA.113.001466. No abstract available.
- Background: PubMed 24835326Fassa AA, Himbert D, Brochet E, Depoix JP, Cheong AP, Alkhoder S, Nataf P, Vahanian A. Transseptal transcatheter mitral valve implantation for severely calcified mitral stenosis. JACC Cardiovasc Interv. 2014 Jun;7(6):696-7. doi: 10.1016/j.jcin.2013.12.204. Epub 2014 May 14. No abstract available.
- Background: PubMed 25240553Ribeiro HB, Doyle D, Urena M, Allende R, Amat-Santos I, Pasian S, Bilodeau S, Mohammadi S, Paradis JM, DeLarochelliere R, Rodes-Cabau J, Dumont E. Transapical mitral implantation of a balloon-expandable valve in native mitral valve stenosis in a patient with previous transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2014 Oct;7(10):e137-9. doi: 10.1016/j.jcin.2014.02.024. Epub 2014 Sep 17. No abstract available.
- Background: PubMed 23847181Ferrari E, Niclauss L, Locca D, Marcucci C. On-pump fibrillating heart mitral valve replacement with the SAPIEN XT transcatheter heart valve. Eur J Cardiothorac Surg. 2014 Apr;45(4):749-51. doi: 10.1093/ejcts/ezt364. Epub 2013 Jul 11.
- Background: PubMed 25500243Himbert D, Bouleti C, Iung B, Nejjari M, Brochet E, Depoix JP, Ghodbane W, Fassa AA, Nataf P, Vahanian A. Transcatheter valve replacement in patients with severe mitral valve disease and annular calcification. J Am Coll Cardiol. 2014 Dec 16;64(23):2557-8. doi: 10.1016/j.jacc.2014.09.047. No abstract available.
- Results publication: PubMed 33888229Guerrero M, Wang DD, Eleid MF, Pursnani A, Salinger M, Russell HM, Kodali SK, George I, Bapat VN, Dangas GD, Tang GHL, Inglesis I, Meduri CU, Palacios I, Reisman M, Whisenant BK, Jermihov A, Kaptzan T, Lewis BR, Tommaso C, Krause P, Thaden J, Oh JK, Douglas PS, Hahn RT, Leon MB, Rihal CS, Feldman T, O'Neill WW. Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):830-845. doi: 10.1016/j.jcin.2021.01.052.
- Results publication: PubMed 33888230Guerrero M, Wang DD, Pursnani A, Salinger M, Russell HM, Eleid M, Chakravarty T, Ng MH, Kodali SK, Meduri CU, Pershad A, Satler L, Waksman R, Palacios I, Smalling R, Reisman M, Gegenhuber M, Kaptzan T, Lewis B, Tommaso C, Krause P, Thaden J, Oh J, Douglas PS, Hahn RT, Kar S, Makkar R, Leon MB, Feldman T, Rihal C, O'Neill WW. Prospective Evaluation of TMVR for Failed Surgical Annuloplasty Rings: MITRAL Trial Valve-in-Ring Arm 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):846-858. doi: 10.1016/j.jcin.2021.01.051.
- Results publication: PubMed 33888231Guerrero M, Pursnani A, Narang A, Salinger M, Wang DD, Eleid M, Kodali SK, George I, Satler L, Waksman R, Meduri CU, Rajagopal V, Inglessis I, Palacios I, Reisman M, Eng MH, Russell HM, Pershad A, Fang K, Kar S, Makkar R, Saucedo J, Pearson P, Bokhary U, Kaptzan T, Lewis B, Tommaso C, Krause P, Thaden J, Oh J, Lang RM, Hahn RT, Leon MB, O'Neill WW, Feldman T, Rihal C. Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. JACC Cardiovasc Interv. 2021 Apr 26;14(8):859-872. doi: 10.1016/j.jcin.2021.02.027.
- Results publication: PubMed 37758379Guerrero ME, Eleid MF, Wang DD, Pursnani A, Kodali SK, George I, Palacios I, Russell H, Makkar RR, Kar S, Satler LF, Rajagopal V, Dangas G, Tang GHL, McCabe JM, Whisenant BK, Fang K, Balan P, Smalling R, Kaptzan T, Lewis B, Douglas PS, Hahn RT, Thaden J, Oh JK, Leon M, O'Neill W, Rihal C. 5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results. JACC Cardiovasc Interv. 2023 Sep 25;16(18):2211-2227. doi: 10.1016/j.jcin.2023.06.041.
- Derived from this study: PubMed 33888232Sticchi A, Reineke D, Praz F, Windecker S. Transcatheter Mitral Valve Replacement for Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Using Balloon-Expandable Transcatheter Heart Valves. JACC Cardiovasc Interv. 2021 Apr 26;14(8):873-878. doi: 10.1016/j.jcin.2021.02.034. No abstract available.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mayra E. Guerrero, MD principal investigator
Mayo Clinic
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcatheter Mitral Valve Replacement in people with Mitral Valve Disease, run by Mayra Guerrero at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Technical Success at Exit From the Cath Lab. (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02370511, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.