TAVR for Aortic Stenosis

(EARLY TAVR Trial)

Recruiting at 77 trial locations

Overseen By Edwards THV Clinical Affairs

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate procedure for TAVR; ongoing for surveillance

901 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety and effectiveness of the Edwards SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve (THV) compared with clinical surveillance (CS) in asymptomatic patients with severe, calcific aortic stenosis.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have conditions that prevent treatment with anti-thrombotic therapy, you may not be eligible to participate.

What data supports the effectiveness of the treatment Edwards SAPIEN 3 / SAPIEN 3 Ultra THV for aortic stenosis?

Research shows that the SAPIEN 3 valve used in TAVR is effective for patients with severe aortic stenosis, especially those at high or intermediate risk for surgery. It has been designed to reduce complications and has shown good short-term outcomes compared to traditional surgical valve replacement. ^{1 2 3 4 5}

Is TAVR with Edwards SAPIEN 3 / SAPIEN 3 Ultra THV safe for humans?

The Edwards SAPIEN 3 valve used in TAVR has shown good short-term safety outcomes in patients with severe aortic stenosis, especially those at high or intermediate surgical risk. The FDA has approved it for high-risk patients, indicating that its benefits outweigh the risks. ^{1 2 3 6 7}

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

The Edwards SAPIEN 3 and SAPIEN 3 Ultra are unique because they are used in transcatheter aortic valve replacement (TAVR), a less invasive procedure compared to traditional open-heart surgery. These devices are designed to reduce complications like paravalvular regurgitation (leakage around the valve) and issues at the vascular access site, making them suitable for patients at high surgical risk. ^{1 2 3 8 9}

Research Team

Philippe Généreux, MD

Principal Investigator

Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation

Eligibility Criteria

This trial is for people aged 65 or older with severe, calcific aortic stenosis who show no symptoms and have an ejection fraction of at least 50%. Participants must be able to give informed consent and have an STS risk score ≤10. It's not for those with symptomatic heart conditions, other diseases requiring surgery, certain valve anomalies, recent heart attacks or strokes, bleeding disorders, severe lung disease or infections like COVID-19.

Inclusion Criteria

I have been diagnosed with severe narrowing of the aortic valve.

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

I do not have any symptoms.

Exclusion Criteria

You have a serious problem with a heart valve called the aortic valve.

I haven't needed heart or lung support machines in the last 30 days.

You have a pre-existing mechanical or bioprosthetic heart valve.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either transcatheter aortic valve replacement (TAVR) or clinical surveillance

Immediate procedure for TAVR; ongoing for surveillance

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary outcomes measured at 2 years

2 years

Treatment Details

Interventions

• Edwards SAPIEN 3 / SAPIEN 3 Ultra THV

Trial Overview The study compares the Edwards SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve (THV) implantation against regular clinical surveillance in patients without symptoms but diagnosed with severe aortic stenosis. The goal is to assess if early intervention with THV improves outcomes compared to just monitoring the condition.

Participant Groups

Group I: TAVR Experimental Treatment 1 Intervention

Transcatheter aortic valve replacement (TAVR)

Group II: CS Active Control 1 Intervention

Clinical surveillance (CS)

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 third generation Sapien 3 device for TAVR showed excellent outcomes, with 92.2% of patients experiencing none or trace paravalvular regurgitation, indicating its efficacy in reducing this complication.

While major vascular complications and bleeding were rare, the study noted a 25.5% rate of permanent pacemaker implantation, suggesting a need for further investigation into this issue in larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome. Murray, MI., Geis, N., Pleger, ST., et al.[2018]

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]

The transcarotid (TC) approach for transcatheter aortic valve replacement (TAVR) using the Edwards Sapien 3 device demonstrated a high procedural success rate of 97% in a study of 314 patients, suggesting it is a viable alternative for those ineligible for transfemoral access.

At 30 days post-procedure, TC-TAVR showed a 3.2% mortality rate and low rates of major complications, including 4.1% major bleeding and 1.6% stroke, indicating that it is a safe option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcarotid Approach for Transcatheter Aortic Valve Replacement With the Sapien 3 Prosthesis: A Multicenter French Registry. Overtchouk, P., Folliguet, T., Pinaud, F., et al.[2020]

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 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]

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

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. [2022]

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

Transcarotid Approach for Transcatheter Aortic Valve Replacement With the Sapien 3 Prosthesis: A Multicenter French Registry. [2020]

6. 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]

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. China pubmed.ncbi.nlm.nih.gov

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

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

Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Balloon-Expandable Transcatheter Heart Valve: A Single-Center Experience. [2016]