Mitral Implantation of TRAnscatheter vaLves

Mitral Valve Disease Clinical Trial

— MITRAL  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02370511
• Other study ID #: 18-006601
• Status: Completed
• Phase: N/A
• Start date: February 25, 2015
• Est. completion date: December 2018

Study information

• Verified date: October 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

Inclusion Criteria in Native Mitral Valve arm

All Candidates must meet the following criteria:

1. 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.

2. Patient is symptomatic from mitral valve disease, as demonstrated by reported NYHA Functional Class II or greater, or symptoms during stress test.

3. The patient is at least 22 years old.

4. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.

5. 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).

6. 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.

7. 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. Inclusion Criteria in Valve-in-Ring arm

All Candidates must meet the following criteria:

1. 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.

2. 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 Inclusion Criteria in Valve-in-Valve arm

All Candidates must meet the following criteria:

1. 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.

2. 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 Exclusion Criteria:

Candidates will be excluded from the study if any of the following conditions are present:

1. Heart Team assessment of operability (the heart team considers the patient is a surgical candidate).

2. 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)].

3. Mitral annulus is not calcified (only applies to patients included in Native MV arm).

4. Complex untreated coronary artery disease:

1. Unprotected left main coronary artery

2. Syntax score > 32 (in the absence of prior revascularization)

5. 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.

6. Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless BMV is a bridge to procedure after a qualifying ECHO).

7. Patients with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation.

8. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt < 50,000 cell/mL).

9. Hypertrophic obstructive cardiomyopathy (HOCM).

10. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation.

11. Need for emergency surgery for any reason.

12. Severe ventricular dysfunction with LVEF < 20%.

13. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.

14. Active upper GI bleeding within 3 months (90 days) prior to procedure.

15. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.

16. 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

17. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure.

18. Estimated life expectancy < 24 months (730 days) due to carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.

19. Expectation that patient will not improve despite treatment of mitral stenosis

20. Active bacterial endocarditis within 6 months (180 days) of procedure.

Related Conditions & MeSH terms

• Heart Valve Diseases
• Mitral Valve Disease

Intervention

Device:
• Transcatheter Mitral Valve Replacement
Implantation of a balloon expandable Edwards SAPIEN XT or SAPIEN 3 transcatheter heart valve in the mitral position.

Locations

Country	Name	City	State
United States	Piedmont HealtCare	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Henry Ford Hospital	Detroit	Michigan
United States	Evanston Hospital / North Shore University HealthSystem	Evanston	Illinois
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Intermountain Medical Center	Murray	Utah
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Banner University Medical Center	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Washington Medical Center	Seattle	Washington
United States	MedStar Washington Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Mayra Guerrero	Henry Ford Hospital

Country where clinical trial is conducted

United States, 

References & Publications (11)

Fassa 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. — View Citation

Ferrari 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. — View Citation

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. — View Citation

Guerrero 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, — View Citation

Guerrero 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, Dougl — View Citation

Guerrero 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 — View Citation

Guerrero 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, — View Citation

Hasan 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. — View Citation

Himbert 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. — View Citation

Ribeiro 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. — View Citation

Sinning 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30 days
Primary	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.	30 days and 1 year
Primary	Mitral Valve Gradient (MVG)	MVG assessed by echocardiography measured in mmHg	30 days and 1 year
Secondary	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.	30 days

External Links

•   Mayo Clinic Clinical Trials