TAVR for Aortic Stenosis

(EARLY TAVR Trial)

Not currently recruiting at 79 trial locations

Overseen By Edwards THV Clinical Affairs

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Must not be taking: Antithrombotics

Disqualifiers: Coronary artery disease, Renal insufficiency, Severe lung disease, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a heart valve replacement procedure called transcatheter aortic valve replacement (TAVR) for individuals with severe aortic stenosis. Aortic stenosis occurs when the heart valve becomes too narrow and stiff, hindering blood flow. The study compares two approaches: using the Edwards SAPIEN 3 heart valve (a type of transcatheter heart valve) or monitoring the condition without immediate surgery. Individuals with severe aortic stenosis who have no symptoms and whose heart is still pumping well might be suitable candidates for this trial. As an unphased trial, it offers patients the chance to contribute to important research that could enhance future treatment options.

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 prior data suggests that the Edwards SAPIEN 3/SAPIEN 3 Ultra THV is safe for patients with aortic stenosis?

Research has shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra Transcatheter Heart Valve (THV) systems are safe for patients. In one study, the SAPIEN 3 Ultra valve showed promising results, with 87% of patients experiencing no or only a tiny leak around the valve after 30 days. This indicates that the valve functioned well and was generally well-tolerated.

Another study found that the SAPIEN 3 Ultra had fewer leaks compared to the earlier version, without increasing the risk of death or other serious issues after one year. The FDA has approved this treatment for patients with heart disease symptoms, underscoring its safety. These findings suggest the procedure is generally safe, with any side effects being minor or manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcatheter Aortic Valve Replacement (TAVR) for aortic stenosis because it offers a minimally invasive alternative to traditional open-heart surgery. Unlike surgical aortic valve replacement, which requires a large chest incision and a longer recovery time, TAVR is performed using a catheter inserted through a small incision, usually in the groin. This method is particularly beneficial for patients who are at high risk for surgical complications. Additionally, the Edwards SAPIEN 3 and SAPIEN 3 Ultra valves used in TAVR are designed to improve fit and function, potentially enhancing patient outcomes and quality of life.

What evidence suggests that the Edwards SAPIEN 3/SAPIEN 3 Ultra THV is effective for aortic stenosis?

Research has shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra Transcatheter Heart Valves (THVs) effectively treat aortic stenosis, a condition where the heart valve narrows. In studies, patients who received these valves experienced significantly lower heart pressure compared to those who received other treatments. After 30 days, only 1% of patients faced serious issues like death or stroke. Additionally, 87% of patients had little to no leaks around the valve, which is a very positive outcome. In this trial, participants in the TAVR arm will receive the SAPIEN 3 or Ultra valves, while those in the clinical surveillance arm will not undergo this intervention. These findings suggest that the SAPIEN 3 and Ultra valves can effectively improve heart function in patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Philippe Généreux, MD

Principal Investigator

Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

1. jacc.org jacc.org/doi/10.1016/j.jcin.2024.02.015

Real-World Outcomes for the Fifth-Generation Balloon ... At discharge, S3UR patients exhibited significantly lower mean gradients (9.2 ± 4.6 mm Hg vs 12.0 ± 5.7 mm Hg; P < 0.0001) and larger aortic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1936879824004618

Real-World Outcomes for the Fifth-Generation Balloon ... The aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes after ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.121.010543

Real-World Experience With the SAPIEN 3 Ultra ... The ultra transcatheter heart valve was associated with similar procedural and 30-day clinical outcomes, but reduced incidence of PVR, compared with S3.

4. eurointervention.pcronline.com eurointervention.pcronline.com/article/thirty-day-outcomes-in-patients-at-intermediate-risk-for-surgery-from-the-sapien-3-european-approval-trial

Thirty-day outcomes in patients at intermediate risk for ... 30-day outcomes of 101 intermediate surgical risk patients treated with the SAPIEN 3 THV via transfemoral route. At 30 days, mortality was 1.0% and stroke ...

5. treatheartvalvefailure.com treatheartvalvefailure.com/hcp/about-tavr-by-edwards/patient-outcomes

Patient Outcomes | Heart Valve Failure HCP The Edwards SAPIEN 3 Ultra valve demonstrated excellent PVL performance with 87% experiencing no/trace PVL at 30 days.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf14/P140031S112B.pdf

FDA - Summary of Safety and Effectiveness Data The Edwards SAPIEN 3 and SAPIEN 3 Ultra THV System is indicated for patients with symptomatic heart disease due to failing (stenosed, insufficient, or combined) ...

7. eurointervention.pcronline.com eurointervention.pcronline.com/article/one-year-outcomes-after-transcatheter-aortic-valve-implantation-with-the-latest-generation-sapien-balloon-expandable-valve-the-s3u-registry

One-year outcomes after transcatheter aortic valve ... A study comparing 1-year outcomes of TAVI using the SAPIEN 3 Ultra vs SAPIEN 3 valves found the S3U reduced paravalvular leak rates without affecting death, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03471065

The SAPIEN 3 Ultra System in Intermediate Risk Patients ... This study will confirm the procedural safety and performance of the SAPIEN 3 Ultra System in subjects with severe, calcific AS who are at intermediate ...

9. eifu.edwards.com eifu.edwards.com/eifu/5970f1a946e0fb00015e5f4c/DOC-0251232B.pdf

Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN 3 Ultra ... Clinical data are not currently available on the INSPIRIS RESILIA aortic valve Model 11500A valve-in-valve procedure or expansion feature. The impact of tissue.