Randomized Trial of Transcatheter Valve-in-Valve vs Redo Surgery for Bioprosthetic Mitral Dysfunction

Randomized Trial of Transcatheter Valve-in-Valve Intervention vs Redo Surgery for the Treatment of Structural Mitral Bioprosthetic Dysfunction

Transcatheter valve-in-valve implantation has emerged as a valid alternative to redo surgery for patients with surgical bioprosthetic dysfunction. Nowadays, transcatheter, transeptal mitral valve-in-valve replacement (TsMViV) has been adopted in many centers worldwide. Some studies report low rates of periprocedural morbidity and mortality and favorable hemodynamic parameters of valve performance. However, medium and long-term data on TsMViV as compared to redo surgical mitral valve replacement (rSMVR) is not yet established. Studies of cost-effectiveness and cost-utility comparing both strategies were also not reported. In particular, late prosthesis durability and hemodynamic performance after TsMViV are largely unknown and need to be elucidated before widely indicated, especially among younger and low-risk surgical candidates with failed mitral bioprostheses.

Study Overview

• Status: Recruiting
• Conditions: Mitral Prosthetic Valve Stenosis and Regurgitation
• Intervention / Treatment: Procedure: Transcatheter Valve-in-Valve Intervention; Procedure: Redo Mitral valve surgery

Detailed Description

Prospective, randomized, controlled trial of transeptal, transcatheter mitral valve-in-valve versus redo surgical mitral valve replacement.

After multidisciplinary, heart team discussion, patients meeting inclusion criteria will be randomized 1:1 to receive either transcatheter, transeptal mitral valve-in-valve replacement (TsMViV) with the SAPIEN 3 transcatheter heart valve (THV) or redo, mitral valve replacement with 3 commercially available surgical bioprosthetic valves. A sub-randomization in the surgical group will define which bioprosthetic valve will be used. Patients will be seen for follow-up visits at discharge, 30 days, 6 months and annually through 10 years.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dimytri Siqueira, MD, PhD; Phone Number: +5511994516856; Email: dimytrisiqueira@gmail.com
• Study Contact Backup: Name: Renata Viana, MD; Phone Number: +551150856325; Email: rviana@dantepazzanese.org.br

Study Locations

• Brazil
  • São Paulo, Brazil, 04012909
    • Recruiting
    • Instituto Dante Pazzanese de Cardiologia
    • Contact: Dimytri A Siqueira, MD, PhD
    • Principal Investigator: DImytri A Siqueira, MD, PhD
    • Principal Investigator: Alexandre A Abizaid, MD, PhD
    • Principal Investigator: Auristela A Ramos, MD, PhD
    • Principal Investigator: Fausto Feres, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age<70 years;
• Symptoms of heart failure NYHA class>ll;
• Severe mitral bioprosthetic dysfunction (stenosis, regurgitation, mixed) defined by echocardiography;
• Heart team (including cardiac surgeon) agree on eligibility including assessment that transeptal, transcatheter mitral valve replacement (TsMVR) and redo surgical mitral valve replacement (rSMVR) are appropriate;
• The study patient or the study patient's legal representative informed of the nature of the study, agreed to its provisions and provided written informed consent as approved by the Institutional Review Board (IRB) center;
• The study patient agreed to comply with all required post- procedure follow-up visits including annual visits through 10 years and analysis close date visits, which was conducted as a phone follow-up;
• Heart team agreed (a priori) on treatment strategy for concomitant coronary disease (if present);
• Patient agreed to undergo redo surgical mitral valve replacement (rSMVR) if randomized to control treatment.

Exclusion Criteria:

• Heart Team assessment of inoperability (including examining cardiac surgeon);
• Hostile chest;
• Evidence of an acute myocardial infarction < 1 month (30 days) before the intended treatment [defined as: Q wave Ml, or non-Q wave Ml with total creatine kinase (CK), creatine kinase MB isoform (CK-MB) and/or cardiac troponin elevations (WHO definition)];
• Concomitant severe valvular disease (aortic, tricuspid or pulmonic) requiring surgical intervention;
• Mitral mechanical prosthesis or mitral valve rings;
• Preexisting mechanical or bioprosthetic valve in other position with dysfunction;
• Complex coronary artery disease: unprotected left main coronary artery, Syntax score > 32 (in the absence of prior 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 an exclusion criteria;
• Patients with planned concomitant surgical or transcatheter ablation for atrial fibrillation;
• Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb< 9 g/dL), thrombocytopenia (Pht< 50,000 cell/mL);
• Hypertrophic cardiomyopathy with or without obstruction (HOCM);
• Severe ventricular dysfunction with left-ventricular ejection fraction (LVEF) < 20%;
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation;
• Active upper gastrointestinal (GI) bleeding within 3 months (90 days) prior to procedure;
• A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure;
• Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 3 months (90 days) of the procedure;
• Renal insufficiency (creatinine > 3.0 mg/dL) and/or renal replacement therapy at the time of screening;
• Estimated life expectancy < 24 months (730 days) due to carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease;
• Currently participating in an investigational drug or another device study;
• Active bacterial endocarditis within 6 months (180 days) of procedure;
• Patient refuses redo mitral valve replacement surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Transcatheter Valve-in-Valve Intervention	Procedure: Transcatheter Valve-in-Valve Intervention; Transcatheter mitral valve-in-valve implantation with SAPIEN 3
OTHER: Redo Surgery; Surgical Mitral valve replacement	Procedure: Redo Mitral valve surgery; Transcatheter Valve-in-Valve Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Major cardiovascular and Cerebrovascular events	All-cause death; Cardiovascular death; Disabling stroke (neurologist assessment)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Procedure-related complications	Major vascular complications; Bleeding and transfusions;; Atrial fibrillation;; Acute renal failure;; Left-ventricular outflow obstruction;; Reoperation	30 days
Rate of Rehospitalization	Rehospitalization at 12 months	12 months
Rate of Prosthetic Thrombosis	Prosthetic thrombosis at 3- and 12 months (as assessed by transesophageal echocardiography and multi-slice tomography).	3 and 12 months
Rate of Structural Valve dysfunction (as assessed by transthoracic echocardiography)	Structural valve dysfunction assessed annually, up to 10-year follow-up.	10 years
Rate of Bioprosthetic Valve Failure (as assessed by clinical outcomes and echocardiographic evaluations)	Bioprosthetic valve failure assessed annually, up to 10-year follow-up.	10 years

Collaborators and Investigators

• Sponsor: Instituto Dante Pazzanese de Cardiologia
• Collaborators: Edwards Lifesciences
• Investigators: Principal Investigator: Dimytri Siqueira, MD, PhD, Instituto Dante Pazzanese de Cardiologia

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 17, 2020
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2031

Study Registration Dates

• First Submitted: May 9, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (ACTUAL): May 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 21, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Mitral Prosthetic valve dysfunction
• Other Study ID Numbers: 4993/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No