TAVI for Heart Valve Disease

(BASELINE Trial)

Recruiting at 14 trial locations

Overseen By Rutger-Jan Nuis, MD, PhD

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Erasmus Medical Center

Disqualifiers: Multi-valve defects, Mechanical aortic valve, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two heart valve replacement options, the Edwards Sapien S3/Ultra bioprosthesis and the Evolut R/PRO bioprosthesis, to determine which performs better for individuals with a worn-out aortic valve. It targets patients who previously underwent an aortic valve replacement that is now failing and require a new one. The trial aims to identify which valve option results in better placement and performance without complications within 30 days. Individuals who have had an aortic valve replacement, are experiencing issues, and are eligible for a transfemoral TAVI (a minimally invasive procedure through the leg) might be suitable candidates for this trial. As an unphased trial, it offers patients the chance to contribute to valuable research that could enhance future heart valve replacement options.

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

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the SAPIEN 3 and SAPIEN 3 Ultra heart valves are generally safe for individuals with heart valve issues. One study found that after a year, these valves had less leakage without affecting survival rates, indicating good safety.

Evidence suggests that the Evolut R and Evolut PRO heart valves are safe in the short term. Specifically, a study on the Evolut PRO demonstrated safety and effectiveness after 30 days. Another study on the Evolut PRO/PRO+ systems confirmed their safety and effectiveness for severe heart valve problems.

Both the SAPIEN and Evolut heart valve systems have been successfully used to treat similar heart conditions. They are well-tolerated, and serious side effects were not a major concern in these studies. This suggests a good safety profile for those considering joining a trial for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for heart valve disease because they offer innovative approaches to valve replacement. The Edwards Sapien S3/Ultra bioprosthesis is unique for its balloon-expanding mechanism, which allows for precise placement and potentially reduces the risk of complications. On the other hand, the Evolut R/PRO bioprosthesis features a self-expanding design, which can lead to a better fit and improved hemodynamics, enhancing blood flow through the heart. These advancements could provide patients with more effective and safer alternatives compared to traditional surgical valve replacement methods.

What evidence suggests that this trial's treatments could be effective for heart valve disease?

This trial will compare the Edwards Sapien S3/Ultra bioprosthesis with the Evolut R/Pro bioprosthesis for treating heart valve disease. Research has shown that the SAPIEN 3 Ultra valve is associated with low death rates and fewer complications within 30 days after the procedure. It also tends to have fewer valve-related issues and a lower need for additional procedures. The Evolut R/Pro valve is known for its long-lasting performance and low rates of significant leakage around the valve. Patients who received the Evolut R/Pro valve experienced low death rates and excellent valve function, even five years after the procedure. Both valves have proven safe and effective for treating severe narrowing of the heart's aortic valve. ^{6 7 8 9 10}

Who Is on the Research Team?

Rutger-Jan Nuis, MD, PhD

Principal Investigator

Erasmus Medical Centre

Prof. Nicolas Van Mieghem

Principal Investigator

Erasmus Medical Centre

Are You a Good Fit for This Trial?

This trial is for patients aged 65 or older with a failing surgical aortic bioprosthesis who need valve replacement and are eligible for transfemoral TAVI. They must be able to give informed consent and have been evaluated by a heart team using imaging techniques.

Inclusion Criteria

I am 65 years old or older.

Written informed consent

My heart valve replacement is failing and I need a new one through a leg artery, as decided by my heart team.

Exclusion Criteria

I have had a stroke or a mini-stroke in the last month.

You have a blood clot in the left ventricle of your heart.

You have a mechanical aortic valve.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo transfemoral TAVI with either SAPIEN-3 / Ultra or Evolut R/Pro

1 day

1 visit (in-person)

Primary Endpoint Evaluation

Evaluation of device success at 30 days post-implantation

30 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including assessment of all-cause death, disabling stroke, and rehospitalization for heart failure or valve-related problems

1 year

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Edwards Sapien S3/Ultra bioprosthesis
• Evolut R/PRO bioprosthesis

Trial Overview The study compares two types of transcatheter heart valves: the balloon-expandable Edwards Sapien S3/Ultra and the self-expanding Evolut R/PRO. It aims to determine which one has better device success at 30 days post-implantation in patients with degenerated bioprostheses.

How Is the Trial Designed?

Group I: Evolut R/Pro bioprosthesis Experimental Treatment 1 Intervention

Study subjects will receive a self-expanding-valve (either the Evolut R or PRO device)

Group II: Edwards Sapien S3/Ultra bioprosthesis Active Control 1 Intervention

Study subjects will receive a balloon-expanding-valve (either the Edwards Sapien S3 or Ultra)

Edwards Sapien S3/Ultra bioprosthesis is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Edwards Sapien S3/Ultra for:

• Severe aortic stenosis
• Degenerated aortic bioprostheses

Approved in United States as Edwards Sapien S3/Ultra for:

• Severe aortic stenosis
• Degenerated aortic bioprostheses

Approved in Canada as Edwards Sapien S3/Ultra for:

• Severe aortic stenosis
• Degenerated aortic bioprostheses

Who Is Running the Clinical Trial?

Erasmus Medical Center

Lead Sponsor

Trials

742

Recruited

2,156,000+

Published Research Related to This Trial

In a review of 6 studies involving 1,664 patients, both the Edwards SAPIEN S3 (ES3) and Medtronic's Evolut R transcatheter heart valves showed similar safety profiles and procedural success rates, with no significant differences in 30-day mortality, stroke, or major complications.

However, the ES3 group had a higher risk of acute kidney injury, while the Evolut R group had a higher rate of new permanent pacemaker implantation, indicating different safety considerations for each device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of third generation balloon-expandable Edwards Sapien 3 versus self-expandable Evolut R in transcatheter aortic valve implantation: a meta-analysis. Li, YM., Tsauo, JY., Liao, YB., et al.[2021]

In a meta-analysis of 21 studies involving 35,248 patients, the Evolut R/Pro valve was linked to a higher risk of short-term all-cause mortality compared to the Sapien 3 valve, indicating potential safety concerns.

While the Evolut R/Pro showed a higher risk of permanent pacemaker implantation and moderate-severe aortic regurgitation, it also had a lower risk of bleeding and major vascular complications, suggesting a complex trade-off in its efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of short- and long-term clinical outcomes of the self-expanding Evolut R/pro valve versus the balloon-expandable Sapien 3 valve for transcatheter aortic valve implantation. Lerman, TT., Levi, A., Kornowski, R.[2022]

In a meta-analysis of 5 studies involving 1460 patients, both Evolut R and Sapien 3 valves showed comparable overall device success rates (95.7% for Evolut R and 94.2% for Sapien 3) and similar short-term complications, including 30-day mortality and stroke rates.

Evolut R demonstrated significantly lower mean and peak aortic valve gradients compared to Sapien 3, suggesting better hemodynamic performance, but further research is needed to clarify differences in paravalvular leakage and pacemaker implantation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of self-expandable Evolut R vs. balloon-expandable Sapien 3 valves for transcatheter aortic valve implantation: A systematic review and meta-analysis. He, C., Xiao, L., Liu, J.[2020]

Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe aortic stenosis who are at moderate to high surgical risk, demonstrating significant efficacy in clinical trials.

Newer-generation devices, such as the SAPIEN-3 and CENTERA valves, have shown improvements in reducing paravalvular leaks and achieving excellent clinical outcomes, indicating advancements in TAVI technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer-generation of Edwards transcatheter aortic valve systems: SAPIEN 3, Centera, and SAPIEN 3 Ultra. Solomonica, A., Choudhury, T., Bagur, R.[2019]

In a study of 232 patients undergoing transcatheter aortic valve implantation, both the Edwards SAPIEN S3 and Medtronic Evolut-R valves showed similar rates of device success and safety at 30 days, with device success rates of 91.9% for SAPIEN S3 and 95.4% for Evolut-R.

However, during follow-up, all-cause mortality was significantly higher in the Evolut-R group compared to the SAPIEN S3 group (7 vs 1 cases), indicating a potential long-term safety concern despite similar short-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Edwards SAPIEN S3 Versus Medtronic Evolut-R Devices for Transcatheter Aortic Valve Implantation. Ben-Shoshan, J., Konigstein, M., Zahler, D., et al.[2022]

In a study involving 995 patients, the new-generation Medtronic Evolut R prosthesis demonstrated a shorter procedure time and lower use of predilatation and contrast dye compared to the older CoreValve, indicating improved efficiency in the TAVI procedure.

Thirty-day clinical outcomes, including rates of complications and mortality, were similar between the Evolut R and CoreValve, suggesting that the new device is as safe and effective as its predecessor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of procedural and clinical outcomes with Evolut R versus Medtronic CoreValve: a Swiss TAVI registry analysis. Noble, S., Stortecky, S., Heg, D., et al.[2020]

In a study of 359 patients aged 82 on average who underwent TAVR with either SAPIEN 3 or Evolut R valves, both devices showed similar rates of device success and 30-day mortality, indicating comparable safety and efficacy.

Long-term survival rates up to 5 years were also similar for both valve types, suggesting that the choice of prosthesis does not significantly impact survival, with comorbidities being the main factors influencing long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome with New Generation Prostheses in Patients Undergoing Transcatheter Aortic Valve Replacement. Tamm, AR., Geyer, M., Kreidel, F., et al.[2021]

The review highlights the clinical outcomes and design features of two leading transcatheter aortic valve replacement (TAVR) valves, the Edwards SAPIEN S3 and Medtronic Evolut PRO+, comparing their effectiveness in treating aortic stenosis based on multiple trials.

While TAVR technology has significantly improved the management of aortic stenosis, ongoing advancements are needed to enhance safety during surgery and to develop more durable valve options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future transcatheter aortic valve replacement valves. Eikelboom, R., Moran, RM., Yan, W., et al.[2023]

Transcatheter aortic valve implantation (TAVI) using the SAPIEN 3™ valve shows improved safety and efficacy by reducing vascular complications and paravalvular leaks compared to earlier models, based on data from the SAPIEN3 trial.

However, the SAPIEN 3™ valve is associated with a higher risk of requiring a permanent pacemaker post-procedure, likely due to its positioning during implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SAPIEN 3 valve: lights and shadows. Facchin, M., Mojoli, M., Covolo, E., et al.[2014]

Citations

1. ir.edwards.com ir.edwards.com/news/news-details/2024/Edwards-SAPIEN-3-Ultra-RESILIA-Valve-Demonstrates-Continued-Excellent-Outcomes-for-Patients-in-Real-World-Data/default.aspx

Edwards' SAPIEN 3 Ultra RESILIA Valve Demonstrates ... Patients receiving the SAPIEN 3 Ultra RESILIA valve experienced extremely low mortality, low rates of reintervention, larger effective orifice ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1936879824017114

1-Year Real-World Outcomes of TAVR With the Fifth ... TAVR with the S3UR is associated with superior 1-year clinical outcomes and lower gradients than its predecessors, with less PVL and low valve reintervention.

3. eurointervention.pcronline.com eurointervention.pcronline.com/article/sapien-3-ultra-balloon-expandable-transcatheter-aortic-valve-in-hospital-and-30-day-results-from-the-multicentre-s3u-registry

In-hospital and thirty-day outcomes of the SAPIEN 3 Ultra ... A study of 139 patients who underwent transfemoral TAVI with the SAPIEN 3 Ultra valve found no deaths or major complications at 30 days, validating design ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf14/P140031S182D.pdf

Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN ... Patients in the trial received a SAPIEN 3 transcatheter heart valve for symptomatic heart disease due to severe native calcific aortic stenosis who were ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9988804/

Cost-Effectiveness of SAPIEN 3 Transcatheter Aortic Valve ... TAVI with SAPIEN 3 appears to be a clinically meaningful, cost-effective treatment option over SAVR for patients with severe symptomatic aortic stenosis and ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf14/P140031S162C.pdf

Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN ... Patients in the trial received a SAPIEN 3 transcatheter heart valve for symptomatic heart disease due to severe native calcific aortic stenosis who were ...

7. edwards.com edwards.com/healthcare-professionals/products-services/transcatheter-heart/transcatheter-sapien-3-ultra

Transcatheter SAPIEN 3 Ultra Built upon the proven SAPIEN platform, the SAPIEN 3 Ultra transcatheter heart valve is designed with your patient's future needs in mind.

8. 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, ...

9. 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) ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02675114

PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN ... 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 ...