SAPIEN X4 THV for Failing Aortic Valves

Recruiting at 33 trial locations

Overseen By Edwards THV Clinical Affairs

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Disqualifiers: Severe mitral regurgitation, Renal insufficiency, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate procedure

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new heart valve treatment called the SAPIEN X4 THV (transcatheter heart valve) to determine its safety and effectiveness for individuals with failing aortic valves. The focus is on those who previously received a valve that is now malfunctioning due to narrowing or leaking and are considered high-risk for surgery. Participants should have a history of moderate to severe valve issues that impact daily life, such as difficulty breathing or fatigue. The trial compares two groups: one receiving a transcatheter heart valve and the other a surgical valve. As an unphased trial, this study allows participants to contribute to important research that could enhance future heart valve treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants must be able to tolerate antithrombotic therapy (medications that prevent blood clots).

What prior data suggests that the SAPIEN X4 THV is safe for use in failing aortic valves?

In a previous study, researchers examined the safety of the SAPIEN X4 Transcatheter Heart Valve (THV) for patients with failing aortic valves. The study aimed to determine if the new heart valve works well and is safe. Although specific safety data isn't provided, the SAPIEN X4 valve resembles other SAPIEN valves already approved for use. This similarity suggests it might be well-tolerated, based on the success of similar devices in the past. However, since this trial is not in an early phase, more detailed safety data will help confirm this. Participants in the study will help gather important information about the safety and effectiveness of this heart valve. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the SAPIEN X4 THV for treating failing aortic valves because it offers a minimally invasive approach through Transcatheter Aortic Valve Replacement (TAVR). Unlike traditional surgical valve replacement, which requires open-heart surgery, TAVR involves threading a catheter through a blood vessel, making it a less invasive option that could mean a quicker recovery for patients. Additionally, the SAPIEN X4 THV can be used to replace both failing transcatheter heart valves and surgical valves, providing a versatile solution for patients who have previously undergone valve replacement. This flexibility and minimally invasive nature are why researchers are eager to explore its potential benefits.

What evidence suggests that the SAPIEN X4 THV is effective for failing aortic valves?

Research shows that the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) holds promise for treating patients with failing aortic valves. In this trial, participants will undergo Transcatheter Aortic Valve Replacement (TAVR) with either the SAPIEN X4 THV for failing aortic transcatheter heart valves or a TAVR for failing aortic surgical valves. Studies have found that the SAPIEN X4 THV can be placed without open-heart surgery, a major benefit for high-risk patients. Early results suggest that the SAPIEN X4 THV performs well for those with a failing aortic bioprosthetic or surgical valve. Specifically, patients using this valve have shown improvements in heart function and quality of life. These findings offer hope for high-risk patients, providing a less invasive option with positive potential outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Pradeep Yadav, MD

Principal Investigator

Piedmont Atlanta Hospital

Robert Cubbedu, MD

Principal Investigator

Naples Community Hospital

Are You a Good Fit for This Trial?

This trial is for adults with a failing aortic bioprosthetic valve who are at high surgical risk. They must have symptoms of heart dysfunction (NYHA class ≥ II) and be suitable for the SAPIEN X4 THV based on their valve size. Participants need to consent to study provisions. Exclusions include unstable valves, severe mitral issues, blood disorders, recent major cardiac events or procedures, pregnancy, certain anatomical features that complicate the procedure, active COVID-19 infection or related sequelae.

Inclusion Criteria

You have a bioprosthetic valve that is the right size for the SAPIEN X4 THV.

You have heart problems that make it difficult for you to do daily activities.

Heart Team agrees the subject is at high or greater surgical risk

Exclusion Criteria

My heart valve replacement doesn't work well, causing high blood pressure in my heart.

The heart valve is not working properly or is damaged.

I am scheduled for a procedure to treat atrial fibrillation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Transcatheter Aortic Valve Replacement (TAVR) with the SAPIEN X4 Transcatheter Heart Valve

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the TAVR procedure

1 year

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• SAPIEN X4 THV

Trial Overview The Edwards SAPIEN X4 Transcatheter Heart Valve (THV) is being tested for safety and effectiveness in patients with failing aortic bioprosthetic valves who face high risks from traditional surgery. The study will evaluate how well this new device works as an alternative to replace dysfunctional heart valves without open-heart surgery.

How Is the Trial Designed?

Group I: Transcatheter Aortic Valve Replacement (TAVR) - THV Experimental Treatment 1 Intervention

TAVR implant in subjects with a failing aortic transcatheter heart valve (THV).

Group II: Transcatheter Aortic Valve Replacement (TAVR) - Surgical Valve Experimental Treatment 1 Intervention

TAVR implant in subjects with a failing aortic surgical valve.

SAPIEN X4 THV is already approved in United States, European Union, Canada for the following indications:

Approved in United States as SAPIEN X4 THV for:

• Severe aortic stenosis in patients at high risk for surgical complications
• Failing aortic bioprosthetic valves

Approved in European Union as SAPIEN X4 THV for:

• Severe aortic stenosis in patients at high risk for surgical complications
• Failing aortic bioprosthetic valves

Approved in Canada as SAPIEN X4 THV for:

• Severe aortic stenosis in patients at high risk for surgical complications
• Failing aortic bioprosthetic valves

Who Is Running the Clinical Trial?

Edwards Lifesciences

Lead Sponsor

Trials

188

Recruited

67,500+

Founded

1958

Headquarters

Irvine, California, U.S.

Known For

Structural Heart Innovations

Top Products

SAPIEN Transcatheter Heart Valve, EVOQUE System, PASCAL Precision, SAPIEN M3

Todd Brinton

Edwards Lifesciences

Chief Medical Officer since 2023

MD from Stanford University

Bernard Zovighian

Edwards Lifesciences

Chief Executive Officer since 2023

MBA from INSEAD

Published Research Related to This Trial

The SAPIEN 3 transcatheter valve demonstrated high safety and efficacy, with 96.4% of patients experiencing none to mild paravalvular regurgitation and a low mortality rate of 2.1% when using the transfemoral approach.

This third-generation valve shows promise as a viable alternative to high- or intermediate-risk surgical options for severe aortic stenosis, particularly due to its improved ease of use and accuracy in positioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter evaluation of a next-generation balloon-expandable transcatheter aortic valve. Webb, J., Gerosa, G., Lefèvre, T., et al.[2022]

In a study of 89 patients undergoing transcatheter aortic valve replacement (TAVR) with the SAPIEN XT valve, low implantation depth was linked to a higher risk of new conduction disturbances and the need for permanent pacemaker implantation.

The study found that while low implantation depth affected heart conduction, the size and expansion of the valve did not lead to similar complications, suggesting that careful positioning of the valve is crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of post-implant SAPIEN XT geometry and position on conduction disturbances, hemodynamic performance, and paravalvular regurgitation. Binder, RK., Webb, JG., Toggweiler, S., et al.[2014]

In a study of 99 patients with severe aortic stenosis undergoing transaortic transcatheter aortic valve implantation (TAVI), both the SAPIEN-XT and SAPIEN-3 valves showed high procedural success and low complication rates, making them effective options for treatment.

The SAPIEN-3 valve demonstrated advantages over the SAPIEN-XT, including shorter fluoroscopy time and a lower need for post-operative dilatation, while both valves had comparable 30-day mortality rates of around 5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transaortic transcatheter aortic valve implantation: experience from the Kiel study. Petzina, R., Lutter, G., Wolf, C., et al.[2018]

The Edwards SAPIENTM transcatheter heart valve (THV) has evolved significantly since its first use in 2007, with improvements in design and delivery systems based on extensive clinical trials and registries, enhancing its safety and efficacy for patients unsuitable for surgery.

Recent advancements, particularly with the SAPIEN XTTM model, have led to better patient selection and procedural techniques, indicating ongoing opportunities for development and optimization in transcatheter aortic valve implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2012 update on the Edwards SAPIENTM transcatheter heart valve. Dworakowski, R., Wendler, O.[2018]

The Edwards SAPIEN transcatheter heart valve (THV) is considered noninferior to traditional surgical aortic valve replacement for high-risk operable patients, based on the high-risk arm of the PARTNER trial.

Despite some concerns about safety and trial misconduct, the FDA panel unanimously agreed that the benefits of the Edwards SAPIEN THV outweigh the risks, leading to its approval for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the 2012 Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee meeting on the Edwards SAPIEN transcatheter heart valve for high-risk aortic stenosis patients. Barbash, IM., Dvir, D., Waksman, R.[2013]

In the MITRAL trial, 30 high-risk patients with failed surgical mitral bioprostheses underwent transseptal mitral valve-in-valve (MViV) using the SAPIEN 3 valve, achieving a 100% technical success rate and low 30-day mortality of 3.3%.

At 1-year follow-up, 82.8% of patients maintained effective valve performance with no significant mitral regurgitation, and 89.3% reported improved symptoms, indicating that this procedure is both safe and effective for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. Guerrero, M., Pursnani, A., Narang, A., et al.[2022]

In a study of 1077 intermediate-risk patients undergoing TAVR with the SAPIEN 3 valve, the 1-year all-cause mortality rate was low at 7.4%, with only 2% experiencing disabling strokes, indicating the procedure's safety and efficacy.

When compared to surgical aortic valve replacement, TAVR demonstrated both non-inferior and superior outcomes for the composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, suggesting it may be the preferred treatment for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Thourani, VH., Kodali, S., Makkar, RR., et al.[2022]

The Sapien 3 transcatheter heart valve (S3-THV) significantly reduced the incidence of at least mild aortic regurgitation (15.9% vs. 46.2%) compared to the previous Sapien XT valve (SXT-THV), indicating improved valve performance.

The S3-THV also showed enhanced safety with no major bleeding or vascular complications reported, while maintaining similar rates of pacemaker implantation and 30-day mortality compared to the SXT-THV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation with the new balloon-expandable Sapien 3 versus Sapien XT valve system: a propensity score-matched single-center comparison. Nijhoff, F., Abawi, M., Agostoni, P., et al.[2016]

In a study of 171 patients treated with transcatheter aortic valve replacement (TAVR) for severe aortic stenosis, both self-expandable CoreValve (CV) and balloon-expandable Edwards SAPIEN XT (ES) showed similar long-term clinical outcomes and hemodynamic performance, with a low rate of prosthesis failure (2.4%).

The mean trans-prosthetic gradient remained stable over five years for both valve types, and the estimated survival rates at 1, 5, and 8 years were 87.6%, 44.9%, and 24.5%, respectively, indicating that both valve types are effective options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes and prosthesis performance after transcatheter aortic valve replacement: results of self-expandable and balloon-expandable transcatheter heart valves. Tarantini, G., Purita, PAM., D'Onofrio, A., et al.[2020]

The SAPIEN XT transcatheter heart valve system is associated with significantly fewer overall and major vascular complications compared to the original SAPIEN system, making it a safer option for patients with severe aortic stenosis who cannot undergo surgery.

Both SAPIEN and SAPIEN XT systems showed similar effectiveness in reducing all-cause mortality, major stroke, and rehospitalization rates at one year, indicating that the newer SAPIEN XT system maintains therapeutic efficacy while improving safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Evaluation of the SAPIEN XT Transcatheter Heart Valve System in Patients With Aortic Stenosis Who Are Not Candidates for Surgery. Webb, JG., Doshi, D., Mack, MJ., et al.[2022]

The SAPIEN XT transcatheter heart valve demonstrated a primary composite safety rate of 12.1% at 30 days in a study of 199 Australian patients with severe aortic stenosis, indicating it is a safe option for those at intermediate surgical risk.

The procedure significantly improved heart function, with 90.9% of patients achieving New York Heart Association class I/II status by 30 days and a reduction in mean aortic gradient from 50.0 mmHg at baseline to 10.3 mmHg at 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance and Safety of Transfemoral TAVI With SAPIEN XT in Australian Patients With Severe Aortic Stenosis at Intermediate Surgical Risk: SOLACE-AU Trial. Yong, G., Walton, T., Ng, M., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05172973

ALLIANCE AVIV: Safety and Effectiveness of the SAPIEN ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05172960

ALLIANCE: Safety and Effectiveness of the SAPIEN X4 ... The objective of this study is to establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects with symptomatic, ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20557493

ALLIANCE AVIV: Safety and Effectiveness of the SAPIEN ... The purpose 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 ...

4. edwards.com edwards.com/patients-care-partners/clinical-research-trials

Clinical Research & Trials The ALLIANCE trial will also explore whether the SAPIEN X4 transcatheter heart valve is beneficial for patients with a failing aortic bioprosthetic valve.

5. withpower.com withpower.com/trial/phase-1a867

SAPIEN X4 THV for Failing Aortic Valves This trial tests a new artificial heart valve that can be inserted without open-heart surgery. It focuses on high-risk patients with failing aortic valves.

6. trialx.com trialx.com/clinical-trials/listings/238267/alliance-aviv-safety-and-effectiveness-of-the-sapien-x4-transcatheter-heart-valve-in-failing-aortic-bioprosthetic-valves/

Safety and Effectiveness of the SAPIEN X4 Transcatheter ... The objective of this study is to establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects ...