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

Trial Summary

What is the purpose of this trial?

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. The valve is placed using a thin tube, making the procedure safer for these patients. This new method offers a less invasive alternative to conventional surgery.

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 data supports the effectiveness of the SAPIEN X4 THV treatment for failing aortic valves?

The SAPIEN 3 valve, a similar treatment, has shown good outcomes in patients with severe aortic stenosis, a condition where the heart's aortic valve narrows, making it hard for blood to flow. This suggests that the SAPIEN X4 THV might also be effective for failing aortic valves. ^{1 2 3 4 5}

Is the SAPIEN X4 THV generally safe for humans?

The Edwards SAPIEN transcatheter heart valve, a predecessor to the SAPIEN X4, has been reviewed for safety in high-risk patients with aortic stenosis, and the benefits were found to outweigh the risks. It has been approved by the FDA for use in patients who are not suitable for surgery, indicating a level of safety in human use. ^{1 3 6 7 8}

What makes the SAPIEN X4 THV treatment unique for failing aortic valves?

The SAPIEN X4 THV is a transcatheter heart valve that offers a minimally invasive option for patients with failing aortic valves, potentially reducing the need for open-heart surgery. It builds on previous versions like the SAPIEN 3 by incorporating features to minimize complications such as aortic regurgitation (leakage of blood back into the heart) and improve the accuracy of valve placement. ^{1 5 9 10 11}

Research Team

Pradeep Yadav, MD

Principal Investigator

Piedmont Atlanta Hospital

Robert Cubbedu, MD

Principal Investigator

Naples Community Hospital

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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 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]

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 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]

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]

References

1. Australia 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. [2022]

3. United States 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. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Impact of post-implant SAPIEN XT geometry and position on conduction disturbances, hemodynamic performance, and paravalvular regurgitation. [2014]

6. United States 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. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

2012 update on the Edwards SAPIENTM transcatheter heart valve. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Transaortic transcatheter aortic valve implantation: experience from the Kiel study. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Multicenter evaluation of a next-generation balloon-expandable transcatheter aortic valve. [2022]

10. United States 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. [2016]

11. China 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. [2020]