ALLIANCE Mitral: Safety and Effectiveness of SAPIEN X4 Transcatheter Heart Valve - Mitral

Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve - Mitral

This study will establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects who are at high or greater surgical risk with a failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring.

Study Overview

• Status: Not yet recruiting
• Conditions: Mitral Regurgitation; Mitral Valve Disease; Mitral Stenosis
• Intervention / Treatment: Device: SAPIEN X4 THV

Detailed Description

This is a prospective, single arm, multicenter, pivotal study.

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edwards THV Clinical Affairs; Phone Number: 949-250-2500; Email: THV_CT.gov@Edwards.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency
2. Bioprosthetic surgical valve or native mitral annulus size suitable for SAPIEN X4 THV
3. NYHA functional class ≥ II
4. Heart Team agrees the subject is at high or greater surgical risk
5. The subject has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent.

Exclusion Criteria:

1. Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system
2. Interatrial septum or left atrium not suitable for transcatheter transseptal access
3. Failing valve has mild or greater paravalvular regurgitation
4. Failing valve is unstable, rocking, or not structurally intact
5. Annuloplasty ring dehiscence
6. Known severe patient-prosthesis mismatch or bioprosthetic valve with residual mean gradient > 10 mmHg at the end of the index procedure for implantation of the original valve
7. Annuloplasty ring type not favorable for THV implantation
8. Increased risk of THV embolization
9. Anatomical characteristics that would increase risk of left ventricular outflow tract (LVOT) obstruction
10. Surgical or transcatheter aortic valve extending into LVOT that may impinge on the mitral implant
11. Severe right ventricle (RV) dysfunction
12. Severe regurgitation or stenosis of any other valve
13. Need for aortic, tricuspid, or pulmonic valve intervention within the next 12 months
14. Left ventricular ejection fraction < 20%
15. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
16. Myocardial infarction within 30 days prior to the study procedure
17. Hypertrophic cardiomyopathy with subvalvular obstruction
18. Subjects with planned concomitant ablation for atrial fibrillation
19. Clinically significant coronary artery disease requiring revascularization
20. Any surgical or transcatheter procedure within 30 days prior to the study procedure. Implantation of a permanent pacemaker or implantable cardioverter defibrillator (ICD) is not considered an exclusion.
21. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure
22. Endocarditis within 180 days prior to the study procedure
23. Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure
24. Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure
25. Renal insufficiency and/or renal replacement therapy
26. Leukopenia, anemia, thrombocytopenia
27. Inability to tolerate or condition precluding treatment with antithrombotic therapy
28. Hypercoagulable state or other condition that increases risk of thrombosis
29. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication
30. Subject refuses blood products
31. Body mass index > 50 kg/m2
32. Estimated life expectancy < 24 months
33. Female who is pregnant or lactating
34. Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
35. Participating in another investigational drug or device study that has not reached its primary endpoint
36. Subject considered to be part of a vulnerable population

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMVR in failing mitral surgical bioprosthetic valve; Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing mitral surgical bioprosthetic valve.	Device: SAPIEN X4 THV; Implantation of the SAPIEN X4 valve
Experimental: TMVR in failing native mitral valve with an annuloplasty ring; Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing native mitral valve with an annuloplasty ring.	Device: SAPIEN X4 THV; Implantation of the SAPIEN X4 valve

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-hierarchical composite of death and stroke at 1 year	The number of patients that died or had a stroke	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline	The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	30 days
Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline	The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	1 year
New York Heart Association (NYHA) functional class compared to 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.	30 days
New York Heart Association (NYHA) functional class compared to 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.	1 year

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Amar Krishnaswamy, MD, The Cleveland Clinic; Principal Investigator: James McCabe, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2038

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 12, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: SAPIEN X4; Valve-in-Valve; Valve-in-Ring
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Mitral Valve Insufficiency; Mitral Valve Stenosis
• Other Study ID Numbers: 2021-05-Mitral

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