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

Официальное название

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.

Обзор

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.

Подробное описание

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).

Вмешательства

• Устройство Transseptal ViMAC
  Transseptal TMVR using balloon-expandable aortic transcatheter valves.

Первичные конечные точки

• Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure [Срок оценки: 1 year.]

Вторичные конечные точки (6)

• Secondary Effectiveness Endpoint [Срок оценки: 1 year]
• Secondary Effectiveness Endpoint [Срок оценки: 1 year.]
• Secondary Effectiveness Endpoint [Срок оценки: 1 year.]
• Secondary Effectiveness Endpoint [Срок оценки: 1 year.]
• Secondary Effectiveness Endpoint [Срок оценки: 1 year.]
• Secondary Effectiveness Endpoint [Срок оценки: 1 year.]

Критерии участия

Критерии включения

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.)
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 16 центров

• Dignity Health Chandler Regional Medical Center — Gilbert
• Banner - University Medicine Cardiology Clinic — Phoenix
• Pima Heart & Vascular — Tucson
• Cedars-Sinai Medical Center — Los Angeles
• Sutter Health — San Francisco
• Uchealth Heart & Vascular Clinic Harmony Campus — Fort Collins
• Medstar Washington Hospital Center — Washington D.C.
• Massachusetts General Hospital — Boston
• … и ещё 8 центров

Мексика · 1 центр

• Ignacio Chávez National Institute of Cardiology — Mexico City

Публикации

• 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
• 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 Cardiov PMID 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. PMID 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. PMID 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. PMID 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, Ker PMID 29699609

Идентификаторы

NCT: NCT04408430 · 20-002438

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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