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

July 24, 2026 updated by: Edwards Lifesciences

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/X4S Transcatheter Heart Valve (THV) in subjects who are at high or greater risk with a failing aortic bioprosthetic valve.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Prospective, single arm, multicenter study

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z1Y6
        • Recruiting
        • St. Paul's Hospital Vancouver
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Recruiting
        • Hamilton Health Sciences
    • Quebec
      • Québec, Quebec, Canada, G1V4G5
        • Recruiting
        • Institut Universitaire de Cardiologie et de Pneumologie de Quebec- Universite Laval
  • 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, 10458
        • Recruiting
        • Montefiore Medical Center
      • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Transcatheter Aortic Valve Replacement (TAVR) - Surgical Valve
TAVR implant in subjects with a failing aortic surgical valve.
Device: SAPIEN X4/X4S THV
Implantation of the SAPIEN X4/X4S valve
Experimental: Transcatheter Aortic Valve Replacement (TAVR) - THV
TAVR implant in subjects with a failing aortic transcatheter heart valve (THV).
Device: SAPIEN X4/X4S THV
Implantation of the SAPIEN X4/X4S valve

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Non-hierarchical composite of death and stroke
Time Frame: 1 year
The number of patients that died or had a stroke
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Time Frame: 30 days
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
Time Frame: 1 year
1 year
New York Heart Association (NYHA) functional class
Time Frame: 30 days
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
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Edwards Lifesciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Robert Cubbedu, MD, Naples Community Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2039

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 14, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 29, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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