SAPIEN X4 THV for Aortic Stenosis

Recruiting at 68 trial locations

Overseen By Edwards THV Clinical Affairs

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Must not be taking: Antithrombotics

Disqualifiers: Renal insufficiency, Stroke, Pregnancy, 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

915 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new heart valve that can be inserted without surgery in patients with severe heart valve narrowing. The new valve helps improve blood flow by replacing the damaged one through a minimally invasive procedure.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the SAPIEN X4 THV treatment for aortic stenosis?

The SAPIEN XT, a predecessor to the SAPIEN X4, has been shown to be effective and safe for patients with severe aortic stenosis who are at high surgical risk, as it was found to be noninferior to surgical valve replacement in high-risk patients. Additionally, the newer Sapien 3 valve, which builds on the SAPIEN XT, has features that improve outcomes, suggesting advancements in the SAPIEN line of valves. ^{1 2 3 4 5}

Is the SAPIEN X4 THV generally safe for humans?

The SAPIEN transcatheter heart valve, including earlier models like the SAPIEN XT, has been evaluated for safety in patients with severe aortic stenosis who are at high surgical risk. The FDA approved it based on trials showing that its benefits outweigh the risks for these patients. ^{1 2 4 6 7}

What makes the SAPIEN X4 THV treatment unique for aortic stenosis?

The SAPIEN X4 THV is a transcatheter heart valve that builds on previous models like the SAPIEN 3, incorporating advanced features to improve safety and effectiveness, such as reducing the risk of vascular injury and paravalvular regurgitation (leakage around the valve). It offers a less invasive alternative to traditional surgical valve replacement, especially for patients who are at high risk for surgery. ^{1 3 5 6 8}

Research Team

Rahul Sharma, MD

Principal Investigator

Stanford University

Tamim M. Nazif, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for individuals with severe, calcified aortic stenosis who are experiencing symptoms and have at least a moderate functional impairment due to the condition. They must understand the study and consent to participate. Exclusions include pregnancy, recent heart attacks or procedures, certain heart diseases, planned surgeries, extreme obesity (BMI > 50), very low life expectancy or ejection fraction, blood disorders, active infections including COVID-19.

Inclusion Criteria

I have severe, calcified aortic stenosis.

The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Your aortic valve size is suitable for the SAPIEN X4 THV.

Exclusion Criteria

I have not had a heart attack in the last 30 days.

I have severe leaking or significant narrowing of my mitral heart valve.

I cannot take blood thinning medications due to my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects undergo transcatheter aortic valve replacement (TAVR)

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits (in-person)

Short-term Follow-up

Participants are monitored for paravalvular leak and new permanent pacemaker implantation

30 days

Treatment Details

Interventions

• SAPIEN X4 THV

Trial Overview The SAPIEN X4 Transcatheter Heart Valve (THV) is being tested for safety and effectiveness in treating symptomatic severe calcific aortic stenosis. The study aims to see if this valve can improve heart function without major surgery by implanting it through a catheter.

Participant Groups

Group I: TAVR - Main Cohort Experimental Treatment 1 Intervention

Subjects will undergo transcatheter aortic valve replacement (TAVR)

Group II: TAVR - Bicuspid Registry Experimental Treatment 1 Intervention

Subjects with bicuspid aortic valve morphology will undergo TAVR

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]

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 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 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]

The Edwards SAPIEN transcatheter heart valve (THV) system offers a less invasive treatment option for severe aortic stenosis, particularly for patients who are inoperable or at high surgical risk, as demonstrated in the pivotal PARTNER trial.

The development of successive models, the XT and S3, aims to enhance procedural outcomes, indicating ongoing improvements in the safety and efficacy of transcatheter heart valve technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve. Minha, S., Waksman, R.[2014]

In a study of 279 patients receiving the Sapien 3 transcatheter heart valve, those with higher implantation positions had significantly lower rates of in-hospital left bundle-branch block (LBBB), indicating better conduction outcomes.

While the implantation zone did not significantly affect the rate of permanent pacemaker implantation or overall mortality at 1 year, positioning the valve higher was associated with fewer conduction abnormalities, suggesting optimal placement may enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reframing Optimal Implantation of the Sapien 3 Transcatheter Heart Valve. Mailey, JA., Brennan, PF., Kearney, A., et al.[2022]

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

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]

3. 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]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve. [2014]

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

Reframing Optimal Implantation of the Sapien 3 Transcatheter Heart Valve. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Edwards SAPIEN 3 valve. [2012]