SAPIEN 3 THV for Aortic Stenosis

(P3 Trial)

Recruiting at 76 trial locations

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Must not be taking: Antithrombotics, Anticoagulants

Disqualifiers: Coronary artery disease, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Expected average of 7 days for hospitalization

1000 Participants Needed

Trial Summary

What is the purpose of this trial?

To establish the safety and effectiveness of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with severe, calcific aortic stenosis who are at low operative risk for standard aortic valve replacement.

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of the treatment SAPIEN 3 THV for Aortic Stenosis?

The SAPIEN 3 valve has shown good outcomes in patients with severe aortic stenosis, reducing the risk of death, stroke, or rehospitalization compared to traditional surgery, especially in those at low to intermediate surgical risk. It also has a design that minimizes complications and improves implantation accuracy. ^{1 2 3 4 5}

Is the SAPIEN 3 THV generally safe for humans?

The SAPIEN 3 transcatheter heart valve (THV) has shown good safety outcomes in patients with severe aortic stenosis, especially those at intermediate risk for surgery. It has been compared to surgical valve replacement and found to have favorable safety profiles in various studies. ^{1 5 6 7 8}

How is the SAPIEN 3 THV treatment for aortic stenosis different from other treatments?

The SAPIEN 3 THV is a transcatheter heart valve that can be implanted without open-heart surgery, making it a less invasive option for treating aortic stenosis. It features a balloon-expandable design with a lower profile cobalt-chromium stent and an additional outer skirt to improve sealing and reduce leaks, which distinguishes it from previous models and traditional surgical valve replacements. ^{1 9 10 11 12}

Research Team

Michael J Mack, MD, FACC

Principal Investigator

The Heart Hospital Baylor Plano, TX

Martin B Leon, MD, FACC

Principal Investigator

Columbia University Medical Center/ New York Presbyterian Hospital, NY

Eligibility Criteria

The PARTNER 3 Trial is for patients with severe, calcified aortic stenosis who are at low risk for standard valve replacement surgery. Participants must have symptoms or test results showing heart function issues and agree to the study's terms. Those with recent strokes, extreme obesity, short life expectancy, refusal of blood products, certain infections or diseases, unsuitable heart valve sizes or conditions that prevent safe procedure completion cannot join.

Inclusion Criteria

A group of heart doctors decides that the patient has a high risk of dying from surgery and has a Society of Thoracic Surgeons (STS) score of less than 4.

I have heart issues affecting my daily activities or exercise ability.

I have severe narrowing of my heart's aortic valve with calcium buildup.

Exclusion Criteria

I have a history of cirrhosis or currently have liver disease.

I have a blood disorder affecting my white cells, red cells, or platelets.

I have not had a stroke or mini-stroke in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either transcatheter heart valve replacement (TAVR) with the Edwards SAPIEN 3 or surgical aortic valve replacement (SAVR)

Expected average of 7 days for hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at discharge, 30 days, 6 months, and annually through 10 years

10 years

Treatment Details

Interventions

• SAPIEN 3 THV

Trial Overview This trial tests the safety and effectiveness of the SAPIEN 3 Transcatheter Heart Valve (THV) compared to standard surgical aortic valve replacement (SAVR). It targets patients with severe aortic stenosis but considered low-risk for traditional surgery. The goal is to see if THV can be an alternative treatment option.

Participant Groups

Group I: Transcatheter aortic valve replacement (TAVR) Experimental Treatment 1 Intervention

Group II: Surgical aortic valve replacement (SAVR) Active Control 1 Intervention

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

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 310 patients undergoing transcatheter aortic valve replacement (TAVR) with either the SAPIEN 3 Ultra or SAPIEN 3 valves, both devices showed high rates of device success and low adverse event rates within 30 days post-procedure.

The SAPIEN 3 Ultra valve demonstrated improved annular sealing properties, resulting in significantly lower rates of mild paravalvular leakage compared to the SAPIEN 3, despite requiring less pre-dilatation during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves: Comparison of SAPIEN 3 Ultra Versus SAPIEN 3. Rheude, T., Pellegrini, C., Lutz, J., et al.[2021]

Transcatheter aortic valve replacement (TAVR) using the SAPIEN 3 valve is a safe and effective alternative to traditional surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis, showing lower rates of complications.

Recent trials have demonstrated that the SAPIEN 3 valve significantly reduces vascular complications and paravalvular leakage, with lower stroke and mortality rates than expected in high-risk surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards SAPIEN 3 Transcatheter Valve For Aortic Stenosis. Htun, NM., Webb, JG.[2016]

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 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 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]

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 85 patients undergoing TAVR with the SAPIEN 3 valve, nonagenarians (aged 90 and above) experienced similar early mortality rates compared to younger patients, indicating that TAVR is a viable option for elderly patients with severe aortic stenosis.

However, nonagenarians had a higher incidence of life-threatening bleeding and major vascular complications (11.8% vs. 1.5% in younger patients), suggesting that while TAVR is safe, older patients may face greater procedural risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians. Ichimoto, E., Arnofsky, A., Wilderman, M., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial. [2023]

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

Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves: Comparison of SAPIEN 3 Ultra Versus SAPIEN 3. [2021]

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

Evaluation of the Edwards SAPIEN 3 Transcatheter Valve For Aortic Stenosis. [2016]

5. France pubmed.ncbi.nlm.nih.gov

Thirty-day outcomes in patients at intermediate risk for surgery from the SAPIEN 3 European approval trial. [2020]

6. 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]

7. 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]

8. 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]

9. 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]

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

Transapical implantation of the SAPIEN 3 valve. [2016]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The first clinical data of the SAPIEN 3 aortic valve in the treatment of aortic stenosis in China. [2023]

12. China pubmed.ncbi.nlm.nih.gov

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians. [2022]