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

NCT04408430 | Recruiting DMC FDA Device

• 1 other identifier: 20-002438
• Study Type: interventional
• Target: 210
• Locations: 2 countries
• Sites: 17

Brief Summary

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.

Conditions

Mitral Annular Calcification; Mitral Stenosis; Mitral Regurgitation; Mitral Valve Disease

Keywords

Transcatheter Mitral Valve Replacement

Outcome Measures

Primary Outcomes (1)

• Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure

  A non-hierarchical composite of all-cause mortality and hospitalization for heart failure.

  1 year.

Secondary Outcomes (6)

• Secondary Effectiveness Endpoint

  1 year

• Secondary Effectiveness Endpoint

  1 year.

• Secondary Effectiveness Endpoint

  1 year.

• Secondary Effectiveness Endpoint

  1 year.

• Secondary Effectiveness Endpoint

  1 year.

Other Outcomes (19)

• Additional Endpoint: Technical Success

  Immediately after the intervention procedure.

• Additional Endpoint: Procedural Success

  30 days

• Additional Endpoint: Device Success

  30 days.

Study Arms (2)

Transseptal ViMAC

EXPERIMENTAL

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

Device: Transseptal ViMAC

Registry of untreated patients

NO INTERVENTION

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

Interventions

Transseptal ViMAC DEVICE

Transseptal TMVR using balloon-expandable aortic transcatheter valves.

Also known as: ViMAC

Transseptal ViMAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Candidates must meet the following criteria:
• \- 18 years of age or older
• 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(+).
• \- NYHA Functional Class ≥II.
• The heart team agrees that valve implantation will likely benefit the patient.
• 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.

You may not qualify if:

• \- The heart team considers the patient is a surgical candidate.
• \- Mitral annulus is not severely calcified.
• \- Myocardial infarction requiring revascularization within 30 days from procedure.
• \- Clinically significant untreated coronary artery disease requiring revascularization.
• 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).
• Severe symptomatic tricuspid regurgitation (hepatic dysfunction, ascites, edema not controlled with diuretics) requiring surgery.
• Leukopenia (WBC \< 3000 cell/mL), acute anemia (Hgb \< 9 g/dL), Thrombocytopenia (Platelets \< 50,000 cell/mL), history of coagulopathy or hypercoagulable state.
• Hypertrophic obstructive cardiomyopathy (HOCM) with mean LVOT gradient of ≥20 mm Hg at rest or ≥50 mmHg with Valsalva.
• 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 left ventricular dysfunction with LVEF \< 20%.
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
• Active upper GI bleeding within 90 days prior to procedure.
• A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
• 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:

Sponsors & Collaborators

• Mayra Guerrero: lead

Study Sites (17)

Dignity Health Chandler Regional Medical Center

Gilbert, Arizona, 85297, United States

RECRUITING

Banner - University Medicine Cardiology Clinic

Phoenix, Arizona, 85006, United States

RECRUITING

Pima Heart & Vascular

Tucson, Arizona, 85712, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Sutter Health

San Francisco, California, 94109, United States

RECRUITING

Uchealth Heart & Vascular Clinic Harmony Campus

Fort Collins, Colorado, 80528, United States

ACTIVE NOT RECRUITING

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 200100, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Columbia University Medical Center/NYPH

New York, New York, 10032, United States

RECRUITING

Oklahoma Heart Institute Utica Office

Tulsa, Oklahoma, 74104, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

University Health

San Antonio, Texas, 78229, United States

RECRUITING

Intermountain Medical Center

Murray, Utah, 84107, United States

RECRUITING

The Sentara Heart Valve and Structural Disease Center

Norfolk, Virginia, 23507, United States

ACTIVE NOT RECRUITING

Ignacio Chávez National Institute of Cardiology

Mexico City, 14080, Mexico

RECRUITING

Related Publications (6)

• 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.

  PMID: 30236304 BACKGROUND

• 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.

  PMID: 28266162 BACKGROUND

• 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.

  PMID: 27377756 BACKGROUND

• 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.

  PMID: 27094423 BACKGROUND

• 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.

  PMID: 24532349 BACKGROUND

• 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.

  PMID: 29699609 RESULT

MeSH Terms

Conditions

Mitral Valve Stenosis; Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Mayra Guerrero, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tatiana Kaptzan, Ph. D.

CONTACT

507-284-1610; kaptzan.tatiana@mayo.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 29, 2020
• Study Start: March 8, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); ME (1)