ALLIANCE: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve

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

The objective of this study is to establish the safety and effectiveness of the Edwards SAPIEN X4/X4S Transcatheter Heart Valve (THV) in subjects with symptomatic, severe, calcific aortic stenosis (AS).

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis, Severe
• Intervention / Treatment: Device: SAPIEN X4 THV; Device: SAPIEN X4S

Detailed Description

This is a prospective, single arm, multicenter study. Subjects with bicuspid aortic valve morphology will be enrolled in a separate registry.

• Study Type: Interventional
• Enrollment (Estimated): 1234
• 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

• Australia
  • Parkville, Australia, 3050
    • Active, not recruiting
    • The Royal Melbourne Hospital
  • Queensland
    • Spring Hill, Queensland, Australia, 4000
      • Active, not recruiting
      • St. Andrews War Memorial Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Active, not recruiting
      • Royal Adelaide Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6E 1M7
      • Active, not recruiting
      • St. Paul's Hospital System
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Active, not recruiting
      • Hamilton Health Services
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Active, not recruiting
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec- Universite Laval
• New Zealand
  • Christchurch, New Zealand, 8011
    • Active, not recruiting
    • Christchurch Hospital
• United States
  • California
    • La Jolla, California, United States, 92037
      • Active, not recruiting
      • Scripps Memorial Hospital La Jolla
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90027
      • Active, not recruiting
      • Kaiser Los Angeles
    • Newport Beach, California, United States, 92663
      • Active, not recruiting
      • Hoag Memorial Hospital Presbyterian
    • Sacramento, California, United States, 95817
      • Active, not recruiting
      • UC Davis Medical Center Sacramento
    • San Francisco, California, United States, 94109
      • Recruiting
      • Bay Area Structural Heart at Sutter Health
    • San Francisco, California, United States, 94115
      • Active, not recruiting
      • Kaiser San Francisco Medical Center
    • Stanford, California, United States, 94305
      • Active, not recruiting
      • Stanford University
  • Colorado
    • Loveland, Colorado, United States, 80538
      • Active, not recruiting
      • UC Health Northern Colorado (Medical Center of the Rockies)
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Active, not recruiting
      • Hartford Hospital
  • Florida
    • North Naples, Florida, United States, 34102
      • Active, not recruiting
      • Naples Community Hospital Healthcare System
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Active, not recruiting
      • Piedmont Heart Institute
    • Atlanta, Georgia, United States, 30322
      • Active, not recruiting
      • Emory University Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Active, not recruiting
      • Rush University Medical Center Chicago
    • Elk Grove Village, Illinois, United States, 60007
      • Recruiting
      • Alexian Brothers Hospital Network
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • NorthShore University HealthSystem Research Institute Evanston
    • Evanston, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Chicago
    • New Lenox, Illinois, United States, 60541
      • Recruiting
      • Silver Cross Hospital
  • Indiana
    • Carmel, Indiana, United States, 46290
      • Active, not recruiting
      • St. Vincent Medical Group, Inc./ St. Vincent Heart Center of Indiana, LLC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Active, not recruiting
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67226
      • Recruiting
      • Ascension Via Christi St. Francis (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
      • Active, not recruiting
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Active, not recruiting
      • Mayo Clinic Rochester
    • Saint Cloud, Minnesota, United States, 56303
      • Active, not recruiting
      • CentraCare Heart and Vascular Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Active, not recruiting
      • Saint Luke's Hospital
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University - Barnes-Jewish Hospital Saint Louis
  • Montana
    • Missoula, Montana, United States, 59802
      • Active, not recruiting
      • St. Patrick Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth-Hitchcock Medical Center, Hanover
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health System Morristown
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Robert Wood Johnson Medical School
    • Ridgewood, New Jersey, United States, 07450
      • Active, not recruiting
      • The Valley Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • University at Buffalo - Kaleida Health
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center/NYPH
    • New York, New York, United States, 10021
      • Recruiting
      • Cornell Medical Center
    • New York, New York, United States, 10458
      • Active, not recruiting
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health and Heart Vascular Institute
    • Charlotte, North Carolina, United States, 28203
      • Active, not recruiting
      • Carolinas Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • The Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Recruiting
      • Oklahoma Cardiovascular Research Group Oklahoma City
    • Tulsa, Oklahoma, United States, 74104
      • Recruiting
      • Oklahoma Heart Institute
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Recruiting
      • Kaiser Portland
    • Portland, Oregon, United States, 97225
      • Active, not recruiting
      • Providence Heart & Vascular Institute Portland
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • Completed
      • Pinnacle Health Harrisburg
    • Pittsburgh, Pennsylvania, United States, 15212
      • Active, not recruiting
      • Allegheny General Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Active, not recruiting
      • Methodist Le Bonheur Healthcare
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Centennial Medical Center
    • Nashville, Tennessee, United States, 37205
      • Recruiting
      • Saint Thomas Health
  • Texas
    • Dallas, Texas, United States, 75230
      • Active, not recruiting
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75226
      • Recruiting
      • Baylor Heart and Vascular Hospital
    • Houston, Texas, United States, 77004
      • Active, not recruiting
      • HCA Houston Healthcare Medical Center
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • University of Texas Memorial Hermann
    • Plano, Texas, United States, 75093
      • Recruiting
      • The Heart Hospital Baylor Plano
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Active, not recruiting
      • Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • Active, not recruiting
      • University of Washington Seattle

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Severe, calcific AS
2. Native aortic annulus size suitable for SAPIEN X4 THV
3. NYHA functional class ≥ II
4. 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. Aortic valve is unicuspid, bicuspid or non-calcified
3. Pre-existing mechanical or bioprosthetic valve in any position
4. Severe aortic regurgitation (> 3+)
5. Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis
6. Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months
7. Left ventricular ejection fraction < 20%
8. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
9. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant PVL after THV implantation
10. Increased risk of coronary artery obstruction after THV implantation
11. Myocardial infarction within 30 days prior to the study procedure
12. Hypertrophic cardiomyopathy with subvalvular obstruction
13. Subjects with planned concomitant ablation for atrial fibrillation
14. Complex coronary artery disease (CAD) that cannot be optimally treated by percutaneous coronary intervention (PCI)
15. Any surgical or transcatheter procedure within 30 days prior to the study procedure (unless part of planned strategy for treatment of CAD). Implantation of a permanent pacemaker or implantable cardioverter defibrillator (ICD) is not considered an exclusion.
16. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure (unless part of planned strategy for treatment of CAD)
17. Endocarditis within 180 days prior to the study procedure
18. Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure
19. Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure
20. Renal insufficiency and/or renal replacement therapy
21. Leukopenia, anemia, thrombocytopenia
22. Inability to tolerate or condition precluding treatment with antithrombotic therapy
23. Hypercoagulable state or other condition that increases risk of thrombosis
24. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication
25. Subject refuses blood products
26. BMI > 50 kg/m2
27. Estimated life expectancy < 24 months
28. Female who is pregnant or lactating
29. Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
30. Participating in another investigational drug or device study that has not reached its primary endpoint
31. 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAVR - Main Cohort; Subjects will undergo transcatheter aortic valve replacement (TAVR)	Device: SAPIEN X4 THV; Implantation of the SAPIEN X4 valve
Experimental: TAVR - Bicuspid Registry; Subjects with bicuspid aortic valve morphology will undergo TAVR	Device: SAPIEN X4 THV; Implantation of the SAPIEN X4 valve
Experimental: TAVR - X4S Registry; Subjects will undergo transcatheter aortic valve replacement (TAVR)	Device: SAPIEN X4S; Implantation of the SAPIEN X4S 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
Favorable outcome per VARC-3: Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥ 60, and 3) KCCQ score decrease ≤10 points from baseline	The number of patients that met all of these criteria. 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
Paravalvular leak	Paravalvular leak will be categorized as None, Trace, Mild, Mild-Moderate, Moderate, Moderate-Severe, or Severe	30 days
New permanent pacemaker implantation	The number of patients with this event	30 days

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Tamim M. Nazif, MD, Columbia University; Principal Investigator: Rahul P. Sharma, MBBS, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2037

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 (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Transcatheter aortic valve implantation (TAVI); Transcatheter aortic valve replacement (TAVR); SAPIEN X4/X4S
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: 2021-05

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