Aortic Stenosis, SevereNCT05172960
ALLIANCE: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve
A study testing SAPIEN X4 THV and SAPIEN X4S in people with Aortic Stenosis, Severe, run by Edwards Lifesciences at 65 sites in 4 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Aortic Stenosis, Severe
- What is being tested?
- SAPIEN X4 THV and SAPIEN X4S
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,234 participants
- Where
- 65 sitesin 4 countries
- Study dates
- 20 Jun 2022to Jan 2037
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Severe, calcific AS
- Native aortic annulus size suitable for SAPIEN X4 THV
- NYHA functional class ≥ II
- The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
Who cannot join
- Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system
- Aortic valve is unicuspid, bicuspid or non-calcified
- Pre-existing mechanical or bioprosthetic valve in any position
- Severe aortic regurgitation (> 3+)
- Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis
- Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months
Show all 31Show fewer
- Left ventricular ejection fraction < 20%
- Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
- Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant PVL after THV implantation
- Increased risk of coronary artery obstruction after THV implantation
- Myocardial infarction within 30 days prior to the study procedure
- Hypertrophic cardiomyopathy with subvalvular obstruction
- Subjects with planned concomitant ablation for atrial fibrillation
- Complex coronary artery disease (CAD) that cannot be optimally treated by percutaneous coronary intervention (PCI)
- 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.
- 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)
- Endocarditis within 180 days prior to the study procedure
- Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure
- Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure
- Renal insufficiency and/or renal replacement therapy
- Leukopenia, anemia, thrombocytopenia
- Inability to tolerate or condition precluding treatment with antithrombotic therapy
- Hypercoagulable state or other condition that increases risk of thrombosis
- Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication
- Subject refuses blood products
- BMI > 50 kg/m2
- Estimated life expectancy < 24 months
- Female who is pregnant or lactating
- Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
- Participating in another investigational drug or device study that has not reached its primary endpoint
- Subject considered to be part of a vulnerable population
Trial locations and contacts
65 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
65 sites in 4 countries
United States58 sites, 31 recruiting
- Active, not recruiting
Piedmont Heart Institute
Atlanta, Georgia, 30309
- Active, not recruiting
Emory University Atlanta
Atlanta, Georgia, 30322
- Recruiting
Medstar Union Memorial Hospital
Baltimore, Maryland, 21218
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
University at Buffalo - Kaleida Health
Buffalo, New York, 14203
- Active, not recruiting
St. Vincent Medical Group, Inc./ St. Vincent Heart Center of Indiana, LLC
Carmel, Indiana, 46290
- Active, not recruiting
Carolinas Health System
Charlotte, North Carolina, 28203
- Recruiting
Novant Health and Heart Vascular Institute
Charlotte, North Carolina, 28204
- Active, not recruiting
Rush University Medical Center Chicago
Chicago, Illinois, 60612
- Recruiting
The Christ Hospital
Cincinnati, Ohio, 45219
- Recruiting
Kaiser Portland
Clackamas, Oregon, 97015
- Active, not recruiting
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
- Recruiting
Baylor Heart and Vascular Hospital
Dallas, Texas, 75226
- Active, not recruiting
Medical City Dallas Hospital
Dallas, Texas, 75230
- Active, not recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
- Recruiting
Alexian Brothers Hospital Network
Elk Grove Village, Illinois, 60007
- Recruiting
NorthShore University HealthSystem Research Institute Evanston
Evanston, Illinois, 60201
- Recruiting
Northwestern University Chicago
Evanston, Illinois, 60611
- Active, not recruiting
Methodist Le Bonheur Healthcare
Germantown, Tennessee, 38138
- Completed
Pinnacle Health Harrisburg
Harrisburg, Pennsylvania, 17101
- Recruiting
Hartford Hospital
Hartford, Connecticut, 06102
- Active, not recruiting
HCA Houston Healthcare Medical Center
Houston, Texas, 77004
- Active, not recruiting
University of Texas Memorial Hermann
Houston, Texas, 77030
- Active, not recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66160
- Active, not recruiting
Saint Luke's Hospital
Kansas City, Missouri, 64111
- Active, not recruiting
Scripps Memorial Hospital La Jolla
La Jolla, California, 92037
- Recruiting
Dartmouth-Hitchcock Medical Center, Hanover
Lebanon, New Hampshire, 03756
- Active, not recruiting
Kaiser Los Angeles
Los Angeles, California, 90027
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
- Active, not recruiting
UC Health Northern Colorado (Medical Center of the Rockies)
Loveland, Colorado, 80538
- Active, not recruiting
St. Patrick Hospital
Missoula, Montana, 59802
- Recruiting
Atlantic Health System Morristown
Morristown, New Jersey, 07960
- Recruiting
Centennial Medical Center
Nashville, Tennessee, 37203
- Recruiting
Saint Thomas Health
Nashville, Tennessee, 37205
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
- Recruiting
Silver Cross Hospital
New Lenox, Illinois, 60541
- Recruiting
Cornell Medical Center
New York, New York, 10021
- Recruiting
Columbia University Medical Center/NYPH
New York, New York, 10032
- Active, not recruiting
Montefiore Medical Center
New York, New York, 10458
- Active, not recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
- Recruiting
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507
- Active, not recruiting
Naples Community Hospital Healthcare System
North Naples, Florida, 34102
- Recruiting
Oklahoma Cardiovascular Research Group Oklahoma City
Oklahoma City, Oklahoma, 73120
- Recruiting
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
- Recruiting
The Heart Hospital Baylor Plano
Plano, Texas, 75093
- Active, not recruiting
Providence Heart & Vascular Institute Portland
Portland, Oregon, 97225
- Active, not recruiting
The Valley Hospital
Ridgewood, New Jersey, 07450
- Active, not recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
- Recruiting
UC Davis Medical Center Sacramento
Sacramento, California, 95817
- Active, not recruiting
CentraCare Heart and Vascular Center
Saint Cloud, Minnesota, 56303
- Recruiting
Bay Area Structural Heart at Sutter Health
San Francisco, California, 94109
- Active, not recruiting
Kaiser San Francisco Medical Center
San Francisco, California, 94115
- Active, not recruiting
University of Washington Seattle
Seattle, Washington, 98195
- Recruiting
Washington University - Barnes-Jewish Hospital Saint Louis
St Louis, Missouri, 63110
- Recruiting
Stanford University
Stanford, California, 94305
- Recruiting
Oklahoma Heart Institute
Tulsa, Oklahoma, 74104
- Recruiting
Ascension Via Christi St. Francis (Cardiovascular Research Institute of Kansas)
Wichita, Kansas, 67226
Australia3 sites
- Active, not recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
- Active, not recruiting
The Royal Melbourne Hospital
Parkville, 3050
- Active, not recruiting
St. Andrews War Memorial Hospital
Spring Hill, Queensland, 4000
Canada3 sites
- Active, not recruiting
Hamilton Health Services
Hamilton, Ontario, L8L 2X2
- Active, not recruiting
Institut Universitaire de Cardiologie et de Pneumologie de Quebec- Universite Laval
Québec, Quebec, G1V 4G5
- Active, not recruiting
St. Paul's Hospital System
Vancouver, British Columbia, V6E 1M7
New Zealand1 site
- Active, not recruiting
Christchurch Hospital
Christchurch, 8011
About this study
Official title: 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).
Read the detailed description
This is a prospective, single arm, multicenter study. Subjects with bicuspid aortic valve morphology will be enrolled in a separate registry.
- Conditions
- Aortic Stenosis, Severe
- Being tested
- SAPIEN X4 THV, SAPIEN X4S
- Keywords
- Transcatheter aortic valve replacement (TAVR), Transcatheter aortic valve implantation (TAVI), SAPIEN X4/X4S
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAPIEN X4 THVDevice
Implantation of the SAPIEN X4 valve
SAPIEN X4SDevice
Implantation of the SAPIEN X4S valve
| Study group | Role | What they receive |
|---|---|---|
| TAVR - Main Cohort | Experimental | Subjects will undergo transcatheter aortic valve replacement (TAVR) Receives: Device: SAPIEN X4 THV |
| TAVR - Bicuspid Registry | Experimental | Subjects with bicuspid aortic valve morphology will undergo TAVR Receives: Device: SAPIEN X4 THV |
| TAVR - X4S Registry | Experimental | Subjects will undergo transcatheter aortic valve replacement (TAVR) Receives: Device: SAPIEN X4S |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-hierarchical composite of death and stroke
The number of patients that died or had a stroke
Measured: 1 year
Secondary outcomes (3)
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.
Measured: 1 year
Paravalvular leak
Paravalvular leak will be categorized as None, Trace, Mild, Mild-Moderate, Moderate, Moderate-Severe, or Severe
Measured: 30 days
New permanent pacemaker implantation
The number of patients with this event
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2021
- Study start20 Jun 2022
- Primary completionJul 2027 (estimated)
- Study completionJan 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic Stenosis, SevereStudies of the same condition, open and under way.
- More trials run by Edwards LifesciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,234 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Edwards Lifesciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tamim M. Nazif, MD, Principal investigator, Columbia UniversityRahul P. Sharma, MBBS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05172960
- Sponsor's protocol ID
- 2021-05
- Status last verified
- Aug 2026
- First submitted
- 14 Dec 2021
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No