The MITRAL II Pivotal Trial (Mitral Implantation of TRAnscatheter vaLves).

NCT ID: NCT04408430

Last Updated: 2026-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-08

Study Completion Date

2030-12-31

Brief Summary

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A prospective multicenter study enrolling high surgical risk patients with severe mitral annular calcification (MAC) and symptomatic mitral valve dysfunction (severe stenosis, ≥ moderate to severe regurgitation, or mixed ≥ moderate stenosis and ≥ regurgitation). There are 2 Arms in this study: 1) "Transseptal (TS) Valve-in-MAC" (ViMAC) Arm, and 2) Natural History of Disease Registry (NHDR) for patients treated with medical treatment only (which includes patients who meet inclusion criteria but can't be treated with transeptal ViMAC due to the presence of anatomical exclusion criteria or other exclusion criteria) and have not had other procedures that may impact outcomes (i.e., alcohol septal ablation or radiofrequency ablation). The study also includes a Registry of Permanently Unassigned" for subjects who undergo preemptive septal ablation procedures (alcohol or radiofrequency) in anticipation of continuing onto ViMAC arm, but are not accepted in the ViMAC Study arm or the patient chooses not to undergo ViMAC procedure.

Detailed Description

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STUDY OBJECTIVE

The purpose of this study is to establish the safety and effectiveness of the Edwards SAPIEN 3, SAPIEN 3 Ultra and SAPIEN 3 Ultra RESILIA (SAPIEN 3/Ultra/RESILIA) valves with Commander delivery system in patients with severe mitral annular calcification and symptomatic mitral valve dysfunction who are not candidates for standard mitral valve surgery.

STUDY DESIGN

A prospective multicenter study enrolling high surgical risk patients with severe mitral annular calcification (MAC) and symptomatic mitral valve dysfunction (severe stenosis, ≥ moderate to severe regurgitation, or mixed ≥ moderate stenosis and ≥ regurgitation). There are 2 arms in this study: 1) "Transseptal (TS) Valve-in-MAC (ViMAC)" arm, 2) Natural History of Disease Registry (NHDR). Patients treated with medical treatment only (which will include patients who meet inclusion criteria but can't be treated with transseptal ViMAC due to the presence of anatomical exclusion criteria or other exclusion criteria) and have not had other procedures that may impact outcomes (i.e. alcohol septal ablation, radiofrequency ablation).

Enrollment Enrollment will consist of 110 patients in the treatment arm (transseptal ViMAC) and up to 100 in the medically treated arm).

Conditions

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Mitral Annular Calcification Mitral Stenosis Mitral Regurgitation Mitral Valve Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Transseptal ViMAC

110 MAC patients treated with transseptal Valve-in-MAC.

Group Type EXPERIMENTAL

Transseptal ViMAC

Intervention Type DEVICE

Transseptal TMVR using balloon-expandable aortic transcatheter valves.

Registry of untreated patients

100 MAC patients not eligible for transseptal ViMAC, treated with conservative management including medications.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Transseptal ViMAC

Transseptal TMVR using balloon-expandable aortic transcatheter valves.

Intervention Type DEVICE

Other Intervention Names

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ViMAC

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayra Guerrero

OTHER

Sponsor Role lead

Responsible Party

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Mayra Guerrero

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Mayra Guerrero, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Dignity Health Chandler Regional Medical Center

Gilbert, Arizona, United States

Site Status RECRUITING

Banner - University Medicine Cardiology Clinic

Phoenix, Arizona, United States

Site Status RECRUITING

Pima Heart & Vascular

Tucson, Arizona, United States

Site Status RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Sutter Health

San Francisco, California, United States

Site Status RECRUITING

Uchealth Heart & Vascular Clinic Harmony Campus

Fort Collins, Colorado, United States

Site Status ACTIVE_NOT_RECRUITING

Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status ACTIVE_NOT_RECRUITING

Columbia University Medical Center/NYPH

New York, New York, United States

Site Status RECRUITING

Oklahoma Heart Institute Utica Office

Tulsa, Oklahoma, United States

Site Status RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

University Health

San Antonio, Texas, United States

Site Status RECRUITING

Intermountain Medical Center

Murray, Utah, United States

Site Status RECRUITING

The Sentara Heart Valve and Structural Disease Center

Norfolk, Virginia, United States

Site Status ACTIVE_NOT_RECRUITING

Ignacio Chávez National Institute of Cardiology

Mexico City, , Mexico

Site Status RECRUITING

Countries

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United States Mexico

Central Contacts

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Tatiana Kaptzan, Ph. D.

Role: CONTACT

507-284-1610

Facility Contacts

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Jennifer Vermillion

Role: primary

Natalie Wiley

Role: backup

Yi Dai

Role: primary

312-237-5891

Adriana Olivares, MD

Role: primary

(520) 324-1560

Khaled Alsabaawi

Role: primary

Milena Ferreira

Role: primary

(415) 600-5707

Eric Collins

Role: primary

202-877-6622

Lina Fu

Role: primary

(617) 643-1371

Sinead Coyle

Role: primary

Kate Dalton

Role: primary

Morgan Panitchpakdi, M.S.

Role: backup

(831) 430-6742

Ashlee Ritter

Role: primary

Zachary Taylor

Role: primary

Rachel Steiner

Role: primary

(210) 743-6453

Sean Moore

Role: backup

Brenda Carroll

Role: primary

Gian Manuel Jimenez Rodriguez, MD

Role: primary

Ruiz Beltran Arturo Maximiliano, MD

Role: backup

References

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Russell HM, Guerrero ME, Salinger MH, Manzuk MA, Pursnani AK, Wang D, Nemeh H, Sakhuja R, Melnitchouk S, Pershad A, Fang HK, Said SM, Kauten J, Tang GHL, Aldea G, Feldman TE, Bapat VN, George IM. Open Atrial Transcatheter Mitral Valve Replacement in Patients With Mitral Annular Calcification. J Am Coll Cardiol. 2018 Sep 25;72(13):1437-1448. doi: 10.1016/j.jacc.2018.07.033.

Reference Type BACKGROUND
PMID: 30236304 (View on PubMed)

Guerrero M, Wang DD, Himbert D, Urena M, Pursnani A, Kaddissi G, Iyer V, Salinger M, Chakravarty T, Greenbaum A, Makkar R, Vahanian A, Feldman T, O'Neill W. Short-term results of alcohol septal ablation as a bail-out strategy to treat severe left ventricular outflow tract obstruction after transcatheter mitral valve replacement in patients with severe mitral annular calcification. Catheter Cardiovasc Interv. 2017 Dec 1;90(7):1220-1226. doi: 10.1002/ccd.26975. Epub 2017 Mar 7.

Reference Type BACKGROUND
PMID: 28266162 (View on PubMed)

Guerrero M, Wang DD, O'Neill W. Percutaneous alcohol septal ablation to acutely reduce left ventricular outflow tract obstruction induced by transcatheter mitral valve replacement. Catheter Cardiovasc Interv. 2016 Nov 15;88(6):E191-E197. doi: 10.1002/ccd.26649. Epub 2016 Jul 5.

Reference Type BACKGROUND
PMID: 27377756 (View on PubMed)

Guerrero M, Urena M, Pursnani A, Wang DD, Vahanian A, O'Neill W, Feldman T, Himbert D. Balloon expandable transcatheter heart valves for native mitral valve disease with severe mitral annular calcification. J Cardiovasc Surg (Torino). 2016 Jun;57(3):401-9.

Reference Type BACKGROUND
PMID: 27094423 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24532349 (View on PubMed)

Guerrero M, Urena M, Himbert D, Wang DD, Eleid M, Kodali S, George I, Chakravarty T, Mathur M, Holzhey D, Pershad A, Fang HK, O'Hair D, Jones N, Mahadevan VS, Dumonteil N, Rodes-Cabau J, Piazza N, Ferrari E, Ciaburri D, Nejjari M, DeLago A, Sorajja P, Zahr F, Rajagopal V, Whisenant B, Shah PB, Sinning JM, Witkowski A, Eltchaninoff H, Dvir D, Martin B, Attizzani GF, Gaia D, Nunes NSV, Fassa AA, Kerendi F, Pavlides G, Iyer V, Kaddissi G, Witzke C, Wudel J, Mishkel G, Raybuck B, Wang C, Waksman R, Palacios I, Cribier A, Webb J, Bapat V, Reisman M, Makkar R, Leon M, Rihal C, Vahanian A, O'Neill W, Feldman T. 1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification. J Am Coll Cardiol. 2018 May 1;71(17):1841-1853. doi: 10.1016/j.jacc.2018.02.054.

Reference Type RESULT
PMID: 29699609 (View on PubMed)

Other Identifiers

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20-002438

Identifier Type: -

Identifier Source: org_study_id

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