MITRAL II Pivotal: Transcatheter mitral valve replacement for severe mitral annular calcification

The Safety and Effectiveness of the Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN 3 Ultra RESILIA (SAPIEN 3/Ultra/RESILIA) Valve in Patients With Symptomatic Severe Calcific Mitral Valve Disease With Severe Mitral Annular Calcification Who Are Not Candidates for Standard Mitral Valve Surgery.

This trial tests whether placing an Edwards SAPIEN transcatheter valve through a transseptal approach helps high-surgical-risk adults with severe mitral annular calcification and symptomatic mitral valve dysfunction.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 210 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (other)
• Locations: 17 sites (Gilbert, Arizona and 16 other locations)
• Trial ID: NCT04408430 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter study enrolling high surgical risk adults with severe mitral annular calcification and symptomatic mitral stenosis, regurgitation, or mixed disease. The treatment arm (Transseptal Valve-in-MAC) uses Edwards SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA valves delivered via a transseptal Commander system, while a Natural History Registry will follow medically managed patients who meet inclusion criteria but are anatomically ineligible for the transseptal procedure. Planned enrollment is about 110 patients in the ViMAC treatment arm and up to 100 in the medically treated registry, with eligibility determined by a multidisciplinary heart team and specific imaging and clinical criteria (e.g., MVA ≤ 1.5 cm2, ≥ moderate to severe MR, NYHA class II or worse). The study focuses on safety and effectiveness outcomes in a population not considered candidates for standard mitral valve surgery.

Who should consider this trial

Good fit: Ideal candidates are adults with severe mitral annular calcification and symptomatic mitral valve dysfunction (severe stenosis or ≥ moderate regurgitation) who are judged high or prohibitive surgical risk and meet anatomical criteria for a transseptal ViMAC procedure.

Not a fit: Patients who have anatomy unsuitable for a transseptal valve-in-MAC approach, who are good candidates for standard surgery, or who have had procedures that affect outcomes (e.g., prior septal ablation) may not benefit from the intervention arm.

Why it matters

Potential benefit: If successful, the approach could offer a less invasive option that reduces symptoms and improves valve function for patients who are poor candidates for open mitral surgery.

How similar studies have performed: Early case series and registries of transcatheter mitral valve replacement in MAC have shown feasibility but variable outcomes and higher complication rates compared with valve-in-valve procedures, so the approach is promising but not yet well established.

Eligibility criteria

Inclusion Criteria:

All Candidates must meet the following criteria:

1. \- 18 years of age or older
2. -Severe mitral annular calcification with symptomatic mitral valve dysfunction including severe mitral stenosis defined as mitral valve area (MVA) of ≤1.5 cm2, or ≥ moderate to severe mitral regurgitation, or mixed ≥ moderated stenosis and ≥ moderate regurgitation. For this study, the severity of mitral regurgitation will be graded according to the 2017 American Society of Echocardiography Guidelines: None, Trivial, Mild 1(+), Moderate 2(+), Moderate to severe 3(+), and severe 4(+).
3. \- NYHA Functional Class ≥II.
4. The heart team agrees that valve implantation will likely benefit the patient.
5. High or prohibitive risk for standard mitral valve surgery as determined by the heart team (at least one site cardiac surgeon must personally examine the subject to determine operative risk in patients presented for inclusion to ViMAC arm). NOTE: Patients not interested in mitral intervention or who are being considered for inclusion in the Natural History of Disease Registry are not required to be evaluated in person by a 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.

Exclusion Criteria for ViMAC subjects (does not apply to the Natural History of Disease Registry):

1. \- The heart team considers the patient is a surgical candidate.
2. \- Mitral annulus is not severely calcified.
3. \- Myocardial infarction requiring revascularization within 30 days from procedure.
4. \- Clinically significant untreated coronary artery disease requiring 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 exclusionary.
6. Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless BMV is a bridge to ViMAC procedure after a qualifying Echo).
7. Severe symptomatic tricuspid regurgitation (hepatic dysfunction, ascites, edema not controlled with diuretics) requiring surgery.
8. Leukopenia (WBC \< 3000 cell/mL), acute anemia (Hgb \< 9 g/dL), Thrombocytopenia (Platelets \< 50,000 cell/mL), history of coagulopathy or hypercoagulable state.
9. Hypertrophic obstructive cardiomyopathy (HOCM) with mean LVOT gradient of ≥20 mm Hg at rest or ≥50 mmHg with Valsalva.
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 left ventricular dysfunction with LVEF \< 20%.
13. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
14. Active upper GI bleeding within 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. Cardiac anatomy that would preclude appropriate delivery and deployment of an Edwards SAPIEN 3/Ultra/RESILIA valve in MAC via transseptal access, including but not limited to:

    * Native neo mitral annulus size \< 275 mm2 or \> 810 mm2 as measured by CT scan.
    * Significant risk of LVOT obstruction or valve embolization as assessed by CT core lab
17. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 90 days of the procedure.
18. Estimated life expectancy \<12 months due to non-cardiac conditions.
19. Expectation that patient will not improve despite treatment of mitral valve dysfunction.
20. Active bacterial endocarditis within 180 days of procedure.
21. \- Severe right ventricular dysfunction as assessed by Echo core lab
22. \- Active infection requiring antibiotic therapy (subject may be a candidate after 2 weeks of antibiotic discontinuation.
23. \- Female who is pregnant or lactating.
24. \- Participating in another investigational device study.
25. \- Aortic valve disease requiring intervention. If aortic valve intervention is required, the AVR procedure should be performed first and if the patient remains symptomatic after AVR, may be presented for consideration for inclusion in this trial.
26. \- Severe fixed pulmonary hypertension (PASP ≥70 mmHg and more than 2/3 of the systemic systolic blood pressure).
27. \- Severe chronic obstructive pulmonary disease requiring continuous home oxygen.
28. \- The patient refuses mitral valve intervention
29. \- Recent symptomatic COVID-19 infection with residual symptoms that may affect the outcomes of this trial.

Where this trial is running

Gilbert, Arizona and 16 other locations

• Dignity Health Chandler Regional Medical Center — Gilbert, Arizona, United States (RECRUITING)
• Banner - University Medicine Cardiology Clinic — Phoenix, Arizona, United States (RECRUITING)
• Pima Heart & Vascular — Tucson, Arizona, United States (RECRUITING)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (RECRUITING)
• Sutter Health — San Francisco, California, United States (RECRUITING)
• Uchealth Heart & Vascular Clinic Harmony Campus — Fort Collins, Colorado, United States (ACTIVE_NOT_RECRUITING)
• Medstar Washington Hospital Center — Washington D.C., District of Columbia, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (ACTIVE_NOT_RECRUITING)
• Columbia University Medical Center/NYPH — New York, New York, United States (RECRUITING)
• Oklahoma Heart Institute Utica Office — Tulsa, Oklahoma, United States (RECRUITING)
• Oregon Health & Science University — Portland, Oregon, United States (RECRUITING)
• University Health — San Antonio, Texas, United States (RECRUITING)
• Intermountain Medical Center — Murray, Utah, United States (RECRUITING)
• The Sentara Heart Valve and Structural Disease Center — Norfolk, Virginia, United States (ACTIVE_NOT_RECRUITING)
• Ignacio Chávez National Institute of Cardiology — Mexico City, Mexico (RECRUITING)

Study contacts

• Principal investigator: Mayra Guerrero, MD — Mayo Clinic
• Study coordinator: Tatiana Kaptzan, Ph. D.

Conditions: Mitral Annular Calcification, Mitral Stenosis, Mitral Regurgitation, Mitral Valve Disease, Transcatheter Mitral Valve Replacement