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Mitral Annular CalcificationMITRAL-IINCT04408430

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

A study testing Transseptal ViMAC in people with Mitral Annular Calcification and Mitral Stenosis, run by Mayra Guerrero at 17 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Transseptal ViMAC
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
17 sitesin 2 countries
Study dates
8 Mar 2021to Dec 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.)
Show all 40Show fewer
  • 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.
  • Exclusion Criteria for ViMAC subjects (does not apply to the Natural History of Disease Registry):
  • - 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 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.
  • 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:
  • 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
  • Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 90 days of the procedure.
  • Estimated life expectancy <12 months due to non-cardiac conditions.
  • Expectation that patient will not improve despite treatment of mitral valve dysfunction.
  • Active bacterial endocarditis within 180 days of procedure.
  • - Severe right ventricular dysfunction as assessed by Echo core lab
  • - Active infection requiring antibiotic therapy (subject may be a candidate after 2 weeks of antibiotic discontinuation.
  • - Female who is pregnant or lactating.
  • - Participating in another investigational device study.
  • - 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.
  • - Severe fixed pulmonary hypertension (PASP ≥70 mmHg and more than 2/3 of the systemic systolic blood pressure).
  • - Severe chronic obstructive pulmonary disease requiring continuous home oxygen.
  • - The patient refuses mitral valve intervention
  • - Recent symptomatic COVID-19 infection with residual symptoms that may affect the outcomes of this trial.

Who cannot join

None listed.

Trial locations and contacts

17 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Tatiana Kaptzan, Ph. D. contact

507-284-1610

kaptzan.tatiana@mayo.edu

17 sites in 2 countries

United States16 sites, 13 recruiting
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Lina Fu, (617) 643-1371, lfu2@mgh.harvard.edu

    Ignacio Inglessis, MD

    Recruiting
  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Sinead Coyle, scoyle3@bwh.harvard.edu

    Pinak Shah, MD

    Recruiting
  • Uchealth Heart & Vascular Clinic Harmony Campus

    Fort Collins, Colorado, 80528

    Active, not recruiting
  • Dignity Health Chandler Regional Medical Center

    Gilbert, Arizona, 85297

    Jennifer Vermillion, jennifer.vermillion@dignityhealth.org

    Natalie Wiley, natalie.wiley@commonspirit.org

    Recruiting
  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Khaled Alsabaawi, Khaled.Alsabaawi@cshs.org

    Raj Makkar, MD

    Recruiting
  • Intermountain Medical Center

    Murray, Utah, 84107

    Brenda Carroll, Brenda.Carroll@imail.org

    Brian Whisenant, MD

    Recruiting
  • Columbia University Medical Center/NYPH

    New York, New York, 10032

    Kate Dalton, keb2114@cumc.columbia.edu

    Morgan Panitchpakdi, M.S., (831) 430-6742, mwp2127@cumc.columbia.edu

    Recruiting
  • The Sentara Heart Valve and Structural Disease Center

    Norfolk, Virginia, 23507

    Active, not recruiting
  • Banner - University Medicine Cardiology Clinic

    Phoenix, Arizona, 85006

    Yi Dai, 312-237-5891, daliseshatz@arizona.edu

    Philip Gideon, MD

    Recruiting
  • Oregon Health & Science University

    Portland, Oregon, 97239

    Zachary Taylor, taylorza@ohsu.edu

    Firars Zahr, MD

    Recruiting
  • Mayo Clinic

    Rochester, Minnesota, 55905

    Active, not recruiting
  • University Health

    San Antonio, Texas, 78229

    Rachel Steiner, (210) 743-6453, Rachel.Steiner@uhtx.com

    Sean Moore, Sean.Moore2@uhtx.com

    Recruiting
  • Sutter Health

    San Francisco, California, 94109

    Milena Ferreira, (415) 600-5707, ferreiml@sutterhealth.org

    David Daniels, MD

    Recruiting
  • Pima Heart & Vascular

    Tucson, Arizona, 85712

    Adriana Olivares, MD, (520) 324-1560, Adriana.Olivares@tmcaz.com

    Thomas E Waggoner, DO

    Recruiting
  • Oklahoma Heart Institute Utica Office

    Tulsa, Oklahoma, 74104

    Ashlee Ritter, ashlee.smithritter@oklahomaheart.com

    Kamran I Muhammad, MD

    Recruiting
  • Medstar Washington Hospital Center

    Washington D.C., District of Columbia, 200100

    Eric Collins, 202-877-6622, erin.c.collins@medstar.net

    Lowell Satler, MD

    Recruiting

Other trials in United States

Mexico1 site, 1 recruiting
  • Ignacio Chávez National Institute of Cardiology

    Mexico City, 14080

    Gian Manuel Jimenez Rodriguez, MD, gian.jimenez@cardiologia.org.mx

    Ruiz Beltran Arturo Maximiliano, MD, arturo.ruiz@cardiologia.org.mx

    Recruiting

Other trials in Mexico

About this study

Official title: 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.

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.

Read the detailed description

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).

Being tested
Transseptal ViMAC
Keywords
Transcatheter Mitral Valve Replacement
Medical subject headings
Mitral Valve Stenosis, Mitral Valve Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transseptal ViMACDevice

    Also called ViMAC

    Transseptal TMVR using balloon-expandable aortic transcatheter valves.

Study groups in NCT04408430
Study groupRoleWhat they receive
Transseptal ViMACExperimental110 MAC patients treated with transseptal Valve-in-MAC.
Receives: Device: Transseptal ViMAC
Registry of untreated patientsNo intervention100 MAC patients not eligible for transseptal ViMAC, treated with conservative management including medications.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year.

Secondary outcomes (6)
  1. Secondary Effectiveness Endpoint

    • Stroke at 30 days and 1 year.

    Measured: 1 year

  2. Secondary Effectiveness Endpoint

    • Change from baseline in New York Heart Association Class at 1 year.

    Measured: 1 year.

  3. Secondary Effectiveness Endpoint

    • Change from baseline in distance walked measure by the 6 Minute Walk Test at 1 year.

    Measured: 1 year.

  4. Secondary Effectiveness Endpoint

    • Change from baseline in quality-of-life measure by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 1 year.

    Measured: 1 year.

  5. Secondary Effectiveness Endpoint

    • Echocardiographic assessment of degree of mitral regurgitation (central and paravalvular) at 1 year.

    Measured: 1 year.

  6. Secondary Effectiveness Endpoint

    • Significant mitral stenosis defined as mean mitral valve gradient by echo > 10 mmHg at 1 year.

    Measured: 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2020
  2. Study start8 Mar 2021
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

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
Parallel groups
Model description
210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.
Masking
None (open label)
Enrolment
210 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04408430
Sponsor's protocol ID
20-002438
Acronym
MITRAL-II
Status last verified
Jan 2026
First submitted
19 May 2020
Last updated
13 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 30236304
  • 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.

    PubMed 28266162
  • 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.

    PubMed 27377756
  • 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.

    PubMed 27094423
  • 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 24532349
  • 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.

    PubMed 29699609

Questions about this trial

What is this clinical trial studying?

A study testing Transseptal ViMAC in people with Mitral Annular Calcification and Mitral Stenosis, run by Mayra Guerrero at 17 sites in 2 countries.

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 40 inclusion and 0 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: looking for participants now, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Mexico. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tatiana Kaptzan, Ph. D. (507-284-1610, kaptzan.tatiana@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure (time frame: 1 year.). 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 NCT04408430, which also lists 6 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 13 Jan 2026.

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