TAVI for Heart Valve Disease

(BASELINE Trial)

Recruiting at 13 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

Trial Summary

What is the purpose of this trial?

Transcatheter aortic valve implantation (TAVI) serves a growing spectrum of patients with symptomatic severe aortic stenosis (AS). Approximately 80% of surgical aortic valve replacements is performed using a bioprosthesis1. Durability of surgical bioprostheses varies based on the patient's age at the moment of implantation, type and size etc2. TAVI has become the preferred treatment for degenerated aortic bioprostheses in elderly patients3. The median time since index surgical aortic valve replacement (SAVR) and for bioprosthetic valve degeneration is typically 8 - 10 years4-6. TAVI in this setting has proven to have equally favorable results as in native aortic valves7. Balloon expandable8 and self-expanding9 transcatheter heart valves (THV) can be used in a degenerated bioprosthesis and each have specific assets and limitations. TAVI in a failed bioprosthesis can cause coronary obstruction, THV migration, paravalvular leakage and prosthesis patient mismatch. The SAPIEN-3 / Ultra and EVOLUT R/Pro are the 2 most commonly used THV platforms in contemporary clinical practice including treatment of failing surgical aortic bioprostheses. Objective: To compare TAVI with EVOLUT R/Pro vs. SAPIEN-3 / Ultra in terms of device success. Study design: International multi-center randomized study with 1:1 randomization to TAVI with SAPIEN-3 / Ultra or Evolut R/Pro. Study population: 440 patients with a failing surgical aortic bioprosthesis (aortic stenosis with or without aortic regurgitation) and selected for transfemoral TAVI by heart-team consensus. Investigational intervention: Transfemoral TAVI with SAPIEN-3 / Ultra or Evolut R/PRO Main study parameters/endpoints: 1. Primary endpoint is device success at 30 days Defined by * Absence of procedural mortality AND * Correct positioning of a single prosthetic heart valve into the proper anatomical location AND * Intended performance of the prosthetic heart valve (no severe prosthesis- patient mismatch and mean aortic valve gradient \< 20 mmHg or peak velocity \< 3 m/s, AND no moderate or severe prosthetic valve regurgitation). Severe prosthesis patient mismatch is defined by effective orifice area (EOAi) ≤0.65 cm2/m2 2. Safety endpoint at 1 year defined by the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems.

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.

What data supports the effectiveness of the treatment Edwards Sapien S3/Ultra bioprosthesis and Evolut R/PRO bioprosthesis for heart valve disease?

Research shows that both the Edwards SAPIEN S3 and Medtronic Evolut R devices have high success rates for transcatheter aortic valve implantation (TAVI), with device success rates of over 90% and low 30-day mortality rates. Long-term outcomes are similar for both devices, with survival mainly influenced by other health conditions. ^{1 2 3 4 5}

Is TAVI generally safe for humans?

Research shows that the Edwards Sapien S3 and Medtronic Evolut R valves used in TAVI are generally safe, with high device success rates and no significant differences in short-term complications like mortality or stroke between the two devices. ^{1 2 3 6 7}

How does the TAVI treatment with Edwards Sapien S3/Ultra and Evolut R/PRO differ from other treatments for heart valve disease?

The TAVI treatment using Edwards Sapien S3/Ultra and Evolut R/PRO is unique because it involves a minimally invasive procedure to replace the heart valve without open-heart surgery, making it suitable for patients at high surgical risk. These newer-generation valves are designed to reduce complications like paravalvular leaks and vascular injuries, offering improved safety and outcomes compared to older valve systems. ^{1 5 6 8 9}

Research Team

Rutger-Jan Nuis, MD, PhD

Principal Investigator

Erasmus Medical Centre

Prof. Nicolas Van Mieghem

Principal Investigator

Erasmus Medical Centre

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

1. China 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. [2021]

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

Comparison of the Edwards SAPIEN S3 Versus Medtronic Evolut-R Devices for Transcatheter Aortic Valve Implantation. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Comparison of procedural and clinical outcomes with Evolut R versus Medtronic CoreValve: a Swiss TAVI registry analysis. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Outcome with New Generation Prostheses in Patients Undergoing Transcatheter Aortic Valve Replacement. [2021]

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

Current and future transcatheter aortic valve replacement valves. [2023]

6. Netherlands 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. [2022]

7. Greece 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Newer-generation of Edwards transcatheter aortic valve systems: SAPIEN 3, Centera, and SAPIEN 3 Ultra. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

The SAPIEN 3 valve: lights and shadows. [2014]