ALLIANCE AVIV: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve in Failing Aortic Bioprosthetic Valves

Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve in Failing Aortic Bioprosthetic Valves

The objective of this study is to establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects who are at high or greater risk with a failing aortic bioprosthetic valve.

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis; Aortic Valve Insufficiency
• Intervention / Treatment: Device: SAPIEN X4 THV

Detailed Description

Prospective, single arm, multicenter study

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

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

Study Locations

• Canada
  • Québec, Canada, G1V4G5
    • Recruiting
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec- Universite Laval
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Recruiting
      • St. Paul's Hospital Vancouver
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
    • San Francisco, California, United States, 94105
      • Recruiting
      • Bay Area Structural Heart at Sutter Health
    • San Francisco, California, United States, 94115
      • Recruiting
      • Kaiser San Francisco
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University Medical Center
  • Colorado
    • Loveland, Colorado, United States, 80538
      • Recruiting
      • UC Health Medical Center of the Rockies
  • Florida
    • Naples, Florida, United States, 34102
      • Recruiting
      • Naples Community Hospital Healthcare System
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Piedmont Heart Institute
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University Atlanta
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Recruiting
      • Northwestern University Chicago
    • Lisle, Illinois, United States, 60532
      • Recruiting
      • Alexian Brothers Hospital Network
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Recruiting
      • Cardiovascular Research Institute of Kansas
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Recruiting
      • MedStar Union Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital Detroit
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health System Morristown
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Robert Wood Johnson University Hospital
    • Ridgewood, New Jersey, United States, 07450
      • Recruiting
      • The Valley Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • University of Buffalo
    • New York, New York, United States, 10021
      • Recruiting
      • Cornelll University New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center / NYPH
    • Rochester, New York, United States, 14621
      • Recruiting
      • Rochester General Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health and Vascular Institute
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Carolinas Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic Foundation
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Recruiting
      • Oklahoma Heart Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny General Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Recruiting
      • Saint Thomas Health
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Memorial Hermann
    • Plano, Texas, United States, 75093
      • Recruiting
      • The Heart Hospital Baylor Plano
  • Washington
    • Seattle, Washington, United States, 98195
      • Withdrawn
      • University of Washington Seattle

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Failing aortic bioprosthetic valve demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency
2. Bioprosthetic valve 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. Failing valve has moderate or severe paravalvular regurgitation
3. Failing valve is unstable, rocking, or not structurally intact
4. Known severe patient-prosthesis mismatch or bioprosthetic valve with residual mean gradient > 20 mmHg at the end of the index procedure for implantation of the original valve
5. Increased risk of THV embolization
6. Surgical or transcatheter valve in the mitral position
7. Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis
8. Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months
9. Left ventricular ejection fraction < 20%
10. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
11. Increased risk of coronary artery obstruction after THV implantation
12. Myocardial infarction within 30 days prior to the study procedure
13. Hypertrophic cardiomyopathy with subvalvular obstruction
14. Subjects with planned concomitant ablation for atrial fibrillation
15. Clinically significant coronary artery disease requiring revascularization
16. Any surgical or transcatheter procedure within 30 days prior to the study procedure. Implantation of a permanent pacemaker or implantable cardioverter defibrillator is not considered an exclusion.
17. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure
18. Endocarditis within 180 days prior to the study procedure
19. Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure
20. Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure
21. Renal insufficiency and/or renal replacement therapy
22. Leukopenia, anemia, thrombocytopenia
23. Inability to tolerate or condition precluding treatment with antithrombotic therapy
24. Hypercoagulable state or other condition that increases risk of thrombosis
25. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication
26. Subject refuses blood products
27. Body mass index > 50 kg/m2
28. Estimated life expectancy < 24 months
29. Female who is pregnant or lactating
30. Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
31. Participating in another investigational drug or device study that has not reached its primary endpoint
32. 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: Transcatheter Aortic Valve Replacement (TAVR) - Surgical Valve; TAVR implant in subjects with a failing aortic surgical valve.	Device: SAPIEN X4 THV; Implantation of the SAPIEN X4 valve
Experimental: Transcatheter Aortic Valve Replacement (TAVR) - THV; TAVR implant in subjects with a failing aortic transcatheter heart valve (THV).	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	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	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
KCCQ score		1 year
New York Heart Association (NYHA) functional class	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
NYHA functional class		1 year

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Pradeep Yadav, MD, Piedmont Atlanta Hospital; Principal Investigator: Robert Cubbedu, MD, Naples Community Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2036

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Transcatheter aortic valve implantation (TAVI); Transcatheter aortic valve replacement (TAVR); SAPIEN X4; Valve-in-valve
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve Insufficiency
• Other Study ID Numbers: 2021-05-AVIV

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
• product manufactured in and exported from the U.S.: No