PARTNER 3 Trial - Mitral Valve in Valve

PARTNER 3 Trial - SAPIEN 3 Transcatheter Heart Valve Implantation in Patients With a Failing Mitral Bioprosthetic Valve

To assess the safety and effectiveness of the SAPIEN 3 transcatheter heart valve in patients with a failing mitral bioprosthetic valve.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Disease
• Intervention / Treatment: Device: Edwards SAPIEN 3 transcatheter valve, Model 9600TFX

Detailed Description

A prospective, single-arm, multicenter clinical trial. This study will enroll patients with symptomatic heart disease due to a failing bioprosthetic mitral valve (stenosed, insufficient, or combined).

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
• Brazil
  • São Paulo
    • Cerqueira César, São Paulo, Brazil, 05403-900
      • Instituto do Coracao da Universidade de Sao Paulo
    • Vila Mariana, São Paulo, Brazil, 04012-909
      • Instituto Dante Pazzanese de Cardiologia
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System Research Institution
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital/ Washington University
  • New York
    • New York, New York, United States, 10016
      • NYU Lagone Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Heart & Vascular Institution
  • Texas
    • Plano, Texas, United States, 75093
      • The Heart Hospital of Baylor Plano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Failing surgically implanted bioprosthetic valve in the mitral position demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency.
2. Surgical bioprosthetic valve with a true internal diameter (True ID) of 16.5 mm to 28.5 mm.
3. NYHA Functional Class ≥ II.
4. Heart Team agrees the patient is intermediate risk (i.e. STS score of ≥3 and < 8).
5. Heart Team agrees valve implantation will likely benefit the patient.
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) / Ethics Committee (EC) of the respective clinical site.

Exclusion Criteria:

1. Index valve has ≥ mild paravalvular regurgitation where the surgical bioprosthesis is not securely fixed in the native annulus or is not structurally intact as determined by transesophageal echocardiography (TEE).
2. Surgical or transcatheter aortic valve placed so that extension into left ventricular outflow tract (LVOT) that may impinge on the mitral implant.
3. Known residual mean gradient >10 mmHg at the end of the index procedure for implantation of the original surgical valve.
4. Severe right ventricle (RV) dysfunction.
5. Anatomical characteristics that would preclude safe access to the apex (transapical).
6. Severe regurgitation or stenosis of any other valve.
7. Severe lung disease (FEV1 < 50% predicted) or currently on home oxygen
8. Severe pulmonary hypertension (e.g., PA systolic pressure ≥ 2/3 systemic pressure)
9. Anatomical characteristics that would increase risk of LVOT obstruction (e.g., aortomitral angle, LVOT size, etc.).
10. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before enrollment.
11. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days prior to the index procedure. Implantation of a permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) is not considered an exclusion.
12. Patients with planned concomitant surgical or transcatheter ablation for atrial fibrillation.
13. Leukopenia (white blood count < 3000 cell/mL), anemia (hemoglobin < 9 g/dL), thrombocytopenia (blood platelet count < 50,000 cell/mL), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
14. Untreated clinically significant coronary artery disease requiring revascularization.
15. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days of enrollment.
16. Emergency intervention/surgical procedures within one month (30 days) prior to the procedure.
17. Any planned surgical, percutaneous coronary, or peripheral procedure to be performed within the 30-day follow-up from the procedure.
18. Hypertrophic cardiomyopathy with obstruction (HOCM).
19. Left ventricular ejection fraction (LVEF) < 30%.
20. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation.
21. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure.
22. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication.
23. Stroke or transient ischemic attack (TIA) within 90 days of enrollment.
24. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of enrollment.
25. Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy at the time of screening.
26. Active bacterial endocarditis within 6 months (180 days) of the procedure.
27. Patient refuses blood products.
28. Estimated life expectancy < 24 months.
29. Currently participating in an investigational drug or another device study. Note: Clinical trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
30. Positive urine or serum pregnancy test in female subjects of childbearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Failing mitral transcatheter valve; Patients with a failing bioprosthetic valve in the mitral position demonstrating stenosis and/or insufficiency will be treated with Edwards SAPIEN 3 transcatheter valve.	Device: Edwards SAPIEN 3 transcatheter valve, Model 9600TFX; Edwards SAPIEN 3 THV system Model 9600TFX with the associated delivery systems.; Other Names: TMVR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Effectiveness - Composite of All-cause Mortality and Stroke	Non-hierarchical composite endpoint of all-cause mortality and stroke at 1-year post-procedure	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New York Heart Association (NYHA) Functional Class - Change From Baseline	NYHA is a functional classification of heart failure based on how much a patient is limited during physical activity. The rating ranges from I - IV, with the lowest (I) as no limitations and the highest (IV) unable to carry on any physical activity without discomfort. A decrease in NYHA class (negative value) shows patient improvement at 30 days.	30 Days
Kansas City Cardiomyopathy Questionnaire (KCCQ) - Change From Baseline	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom, social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. An increase in KCCQ score (positive value) shows patient improvement at 30 days.	30 days
Mitral Regurgitation - Change From Baseline	Echocardiographic assessment of the degree of mitral valve regurgitation None=0, Trace=0.5, Mild or Mild-Moderate=1, Moderate=2, Moderate-Severe=3, and Severe=4. A decrease in MR (negative value) shows patient improvement at 30 days.	30 days
Pulmonary Artery Systolic Pressure - Change From Baseline	Echocardiographic assessment of pulmonary artery systolic pressure A decrease in pulmonary artery systolic pressure (negative value) shows patient improvement at 30 days.	30 days

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Chris S. Malaisrie, MD, Northwestern University Feinberg School of Medicine; Principal Investigator: Mayra Guerrero, MD, Mayo Clinic; Principal Investigator: Alan Zajarias, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Malaisrie SC, Guerrero M, Davidson C, Williams M, de Brito FS Jr, Abizaid A, Shah P, Kaneko T, Poon K, Levisay J, Yu X, Pibarot P, Hahn RT, Blanke P, Leon MB, Mack MJ, Zajarias A; PARTNER 3 Mitral Valve-in-Valve Study Investigators. One-Year Outcomes of Transseptal Mitral Valve-in-Valve in Intermediate Surgical Risk Patients. Circ Cardiovasc Interv. 2024 Aug;17(8):e013782. doi: 10.1161/CIRCINTERVENTIONS.123.013782. Epub 2024 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): August 16, 2022
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 21, 2017

Study Record Updates

• Last Update Posted (Estimated): November 5, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: cardiovascular disease; TMVR; SAPIEN 3; PARTNER 3; failing valve; failing bioprosthetic valve
• Additional Relevant MeSH Terms: Heart Diseases; Heart Valve Diseases; Heart Failure; Cardiovascular Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 2015-08 MVIV

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: Yes