Mitral RegurgitationNCT06167213
ALLIANCE Mitral: Safety and Effectiveness of SAPIEN X4 Transcatheter Heart Valve - Mitral
A study testing SAPIEN X4 THV in people with Mitral Regurgitation and Mitral Valve Disease, run by Edwards Lifesciences.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mitral Regurgitation, Mitral Valve Disease, Mitral Stenosis
- What is being tested?
- SAPIEN X4 THV
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- No sites listed yet
- Study dates
- Jan 2027to Mar 2038
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency
- Bioprosthetic surgical valve or native mitral annulus size suitable for SAPIEN X4 THV
- NYHA functional class ≥ II
- Heart Team agrees the subject is at high or greater surgical risk
- 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
- Interatrial septum or left atrium not suitable for transcatheter transseptal access
- Failing valve has mild or greater paravalvular regurgitation
- Failing valve is unstable, rocking, or not structurally intact
- Annuloplasty ring dehiscence
- 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
Show all 36Show fewer
- Annuloplasty ring type not favorable for THV implantation
- Increased risk of THV embolization
- Anatomical characteristics that would increase risk of left ventricular outflow tract (LVOT) obstruction
- Surgical or transcatheter aortic valve extending into LVOT that may impinge on the mitral implant
- Severe right ventricle (RV) dysfunction
- Severe regurgitation or stenosis of any other valve
- Need for aortic, tricuspid, or pulmonic valve intervention within the next 12 months
- Left ventricular ejection fraction < 20%
- Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
- Myocardial infarction within 30 days prior to the study procedure
- Hypertrophic cardiomyopathy with subvalvular obstruction
- Subjects with planned concomitant ablation for atrial fibrillation
- Clinically significant coronary artery disease requiring revascularization
- 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.
- Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure
- 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
- Body mass index > 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
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
Read the detailed description
This is a prospective, single arm, multicenter, pivotal study.
- Conditions
- Mitral Regurgitation, Mitral Valve Disease, Mitral Stenosis
- Being tested
- SAPIEN X4 THV
- Keywords
- SAPIEN X4, Valve-in-Valve, Valve-in-Ring
- Medical subject headings
- Mitral Valve Insufficiency, Mitral 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
| Study group | Role | What they receive |
|---|---|---|
| TMVR in failing mitral surgical bioprosthetic valve | Experimental | Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing mitral surgical bioprosthetic valve. Receives: Device: SAPIEN X4 THV |
| TMVR in failing native mitral valve with an annuloplasty ring | Experimental | Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing native mitral valve with an annuloplasty ring. Receives: Device: SAPIEN X4 THV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-hierarchical composite of death and stroke at 1 year
The number of patients that died or had a stroke
Measured: 1 year
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2023
- Study startJan 2027 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionMar 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitral RegurgitationStudies 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
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Edwards Lifesciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amar Krishnaswamy, MD, Principal investigator, The Cleveland ClinicJames McCabe, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06167213
- Sponsor's protocol ID
- 2021-05-Mitral
- Status last verified
- Dec 2025
- First submitted
- 4 Dec 2023
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve - Mitral
- ClinicalTrials.gov ID
- NCT06167213
- Acronym / sponsor ID
- 2021-05-Mitral
- Conditions
- Mitral Regurgitation, Mitral Valve Disease, Mitral Stenosis
- Keywords
- SAPIEN X4, Valve-in-Valve, Valve-in-Ring
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Edwards LifesciencesIndustry (pharma, biotech, devices)
- Study start
- Jan 2027 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2038 (estimated)
- First posted
- 12 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, single arm, multicenter, pivotal study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TMVR in failing mitral surgical bioprosthetic valve | Experimental | Device: SAPIEN X4 THVTranscatheter Mitral Valve Replacement (TMVR) in subjects with a failing mitral surgical bioprosthetic valve. |
| TMVR in failing native mitral valve with an annuloplasty ring | Experimental | Device: SAPIEN X4 THVTranscatheter Mitral Valve Replacement (TMVR) in subjects with a failing native mitral valve with an annuloplasty ring. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency
- Bioprosthetic surgical valve or native mitral annulus size suitable for SAPIEN X4 THV
- NYHA functional class ≥ II
- Heart Team agrees the subject is at high or greater surgical risk
- The subject has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent.
Key exclusion criteria (36 listed)
- Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system
- Interatrial septum or left atrium not suitable for transcatheter transseptal access
- Failing valve has mild or greater paravalvular regurgitation
- Failing valve is unstable, rocking, or not structurally intact
- Annuloplasty ring dehiscence
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAPIEN X4 THVImplantation of the SAPIEN X4 valve | Device | TMVR in failing mitral surgical bioprosthetic valve, TMVR in failing native mitral valve with an annuloplasty ring |
Primary outcome
Non-hierarchical composite of death and stroke at 1 year
Time frame: 1 year
The number of patients that died or had a stroke
4 secondary outcomes
Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline
Time frame: 30 days
Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline
Time frame: 1 year
New York Heart Association (NYHA) functional class compared to baseline
Time frame: 30 days
New York Heart Association (NYHA) functional class compared to baseline
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amar Krishnaswamy, MD principal investigator
The Cleveland Clinic
James McCabe, MD principal investigator
University of Washington
Questions about this trial
What is this clinical trial studying?
A study testing SAPIEN X4 THV in people with Mitral Regurgitation and Mitral Valve Disease, run by Edwards Lifesciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Edwards THV Clinical Affairs (949-250-2500, THV_CT.gov@edwards.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-hierarchical composite of death and stroke at 1 year (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.