MRI-Guided Valve Replacement for Aortic Valve Stenosis

(MRI-TAVR Trial)

Overseen By LaStasha Cowan

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Hospitals Cleveland Medical Center

Disqualifiers: Pacemakers, Defibrillators, Claustrophobia, Arrhythmia, others

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

Compensation: Varies

Number of Visits: 5

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of heart valve replacements for individuals with aortic valve stenosis, a condition where the heart's valve doesn't open fully. One group will receive a balloon-expanding valve (Edwards Sapien 3 Ultra), while the other will receive a self-expanding valve (Medtronic Evolut FX). The researchers aim to determine which valve improves blood flow more effectively, particularly during exercise. Suitable participants should require a valve replacement and be able to undergo tests like an exercise bike stress test. As an unphased trial, this study allows participants to contribute to valuable research that could enhance future heart valve treatments.

Will I have to stop taking my current medications?

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 prior data suggests that this MRI-guided valve replacement technique is safe for aortic valve stenosis?

Research has shown that both the Edwards Sapien 3 Ultra and the Medtronic Evolut FX heart valves are generally safe for patients needing heart valve replacements.

For the Edwards Sapien 3 Ultra, a study with 139 patients found no deaths or major problems in the first 30 days after implantation, suggesting the valve is well-tolerated shortly after placement.

The Medtronic Evolut FX valve also demonstrates good safety results. Early reports from its use in patients with severe aortic valve narrowing showed high success rates and few complications. Another study found that the Evolut system performed well and lasted up to five years in patients with low-risk aortic valve narrowing.

These findings reassure the immediate and longer-term safety of both valve types in heart procedures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for aortic valve stenosis because they offer innovative approaches to valve replacement. The balloon-expanding Edwards Sapien 3 Ultra valve uses a unique balloon mechanism that allows precise placement and secure expansion within the heart. On the other hand, the self-expanding Medtronic Evolut FX valve adapts to the anatomy of the aorta over time, ensuring a snug fit and potentially enhancing long-term outcomes. Both methods are designed to be less invasive than traditional open-heart surgery, promising quicker recovery times and reduced risk for patients.

What evidence suggests that this trial's treatments could be effective for aortic valve stenosis?

This trial will compare two different valves for transcatheter aortic valve replacement (TAVR) in treating aortic valve stenosis. Research has shown that the Edwards Sapien 3 Ultra valve, which is expanded using a balloon, effectively treats aortic valve narrowing. Studies indicate it has lower pressure differences across the valve and fewer leaks around the valve compared to older models. In a study with 139 patients, no deaths or major complications occurred within 30 days after the procedure.

Meanwhile, the Medtronic Evolut FX valve, which expands on its own, also shows promising early results. Patients have experienced good outcomes and excellent valve performance for up to five years after the procedure. The valve demonstrated high success rates and low complication rates in treating severe aortic valve narrowing. Both valves are strong options being evaluated in this trial for those considering treatment for this condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Guilherme Attizzani, MD

Principal Investigator

UH, Cleveland Medical Center

Sadeer Al-Kindi, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with aortic valve stenosis who need a valve replacement and can undergo the procedure through their leg artery. They must be able to consent, have no severe heart issues like reduced heart function or untreated coronary disease, no history of valve replacements, and no implants that are unsafe for MRI.

Inclusion Criteria

I am over 18 and scheduled for a transfemoral TAVR procedure.

My heart team has decided I need a valve replacement due to aortic valve stenosis.

Able to give informed consent

Exclusion Criteria

I have untreated heart artery problems.

I have had a surgical aortic valve replacement or a valve-in-valve TAVR procedure.

My heart's pumping ability is reduced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-TAVR MRI

CMR performed up to three months prior to the TAVR procedure to assess baseline cardiac function

Up to 12 weeks

TAVR Procedure

Participants undergo transcatheter aortic valve replacement with either the self-expanding valve Evolut FX or the balloon-expandable valve Sapien 3 Ultra

1 day

1 visit (in-person)

Post-TAVR Monitoring

Participants are monitored with echocardiography immediately post TAVR, 1-day post TAVR, and at 30-days post TAVR

30 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up CMR at 1-year

1 year

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Balloon-expanding valve (Edwards Sapien 3 Ultra)
• Self-expanding valve (Medtronic Evolut FX)

Trial Overview The study tests if self-expanding valves (Medtronic Evolut FX) provide better blood flow and exercise capacity compared to balloon-expanding valves (Edwards Sapien 3 Ultra), using stress cardiac MRI to measure differences in heart performance.

How Is the Trial Designed?

Group I: TAVR using the self-expanding valve Evolut FX Active Control 1 Intervention

Transcatheter aortic valve replacement (TAVR) using the bioprosthesis Medtronic Evolut FX supra-annular self-expanding valve

Group II: TAVR using the balloon-expandable valve Sapien 3 Ultra Active Control 1 Intervention

Transcatheter aortic valve replacement (TAVR) using the bioprosthesis Edwards Sapien 3 Ultra valve

Balloon-expanding valve (Edwards Sapien 3 Ultra) is already approved in United States, European Union for the following indications:

Approved in United States as Edwards Sapien 3 Ultra for:

• Severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency

Approved in European Union as Edwards Sapien 3 Ultra for:

• Severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency
• Degenerated bioprosthetic aortic valve

Who Is Running the Clinical Trial?

University Hospitals Cleveland Medical Center

Lead Sponsor

Trials

348

Recruited

394,000+

Guilherme Attizzani, MD

Lead Sponsor

Trials

1

Recruited

90+

Published Research Related to This Trial

In a study of 563 patients undergoing transcatheter aortic valve replacement (TAVR) with either balloon-expandable (BE) or self-expandable (SE) valves, the SE valves were associated with a higher risk of ischemic stroke at 30 days (6.0% vs 1.4%), although other outcomes like mortality and readmission rates were similar between the two types.

Midterm outcomes for both BE and SE valves were comparable, suggesting that while SE valves may pose a short-term stroke risk, overall survival and readmission rates do not significantly differ, indicating that patient selection based on clinical factors is important for optimal valve choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Current-Generation Transfemoral Balloon-Expandable Versus Self-Expandable Transcatheter Aortic Valve Replacement. Habertheuer, A., Gleason, TG., Kilic, A., et al.[2021]

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]

The self-expanding transcatheter heart valve (Medtronic Cardiovascular Corevalve and Evolut) has been significantly improved in design and technique, enhancing its safety, efficacy, and durability for patients with severe aortic stenosis.

This valve is particularly advantageous for patients with varying levels of surgical risk and preliminary data indicates that its durability is comparable to that of traditional surgical tissue valves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis. Hughes, E., Grossman, PM.[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]

In a study of 66 patients comparing two types of transcatheter aortic valves, the Evolut R valve consistently showed lower mean gradients than the Sapien 3 valve at all follow-up points (1 year, 6 months, and discharge), indicating better hemodynamic performance.

Smaller sizes of both valve types were associated with higher gradients, but the Evolut R valve maintained superior performance over the Sapien 3, suggesting that valve size and type significantly impact patient outcomes post-implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 1-year Follow-up Echocardiographic Outcomes of Sapien 3 Versus Evolut R Bioprosthetic Transcatheter Aortic Valves: A Single-center Retrospective Iranian Cohort Study. Sahebjam, M., Zoroufian, A., Hajizeinali, A., et al.[2023]

The Medtronic CoreValve Evolut R 34 mm, the largest self-expanding transcatheter heart valve, demonstrated a high procedural success rate of 92.1% in a study of 101 patients, indicating its efficacy in treating aortic stenosis.

The early safety profile was favorable, with a low 30-day mortality rate of 2.0% and a low incidence of major complications, including only 1.0% major vascular complications and 5.0% bleeding events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation with the 34 mm self-expanding CoreValve Evolut R: initial experience in 101 patients from a multicentre registry. Kuhn, C., Frerker, C., Meyer, AK., et al.[2019]

The Sapien 3 transcatheter heart valve (S3 THV) was successfully implanted in 54 high-risk patients with aortic stenosis, showing excellent clinical outcomes with 97.8% of patients experiencing no or mild aortic regurgitation at 30 days post-procedure.

The study reported a low incidence of complications, with only 3.7% of patients experiencing stroke or all-cause mortality, and all patients improved to New York Heart Association Functional Class I or II, indicating significant functional improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Incidence of Paravalvular Leakage With the Balloon-Expandable Sapien 3 Transcatheter Heart Valve. Wendt, D., Al-Rashid, F., Kahlert, P., et al.[2022]

In a study involving 177 patients who underwent transcatheter aortic valve replacement (TAVR), the self-expandable Portico valve and the balloon-expandable Sapien 3 valve showed similar short-term clinical outcomes, with no significant differences in 30-day mortality or major complications.

While procedural success rates were nearly identical (99.0% for Portico vs 98.6% for Sapien 3), the Sapien 3 valve required significantly less contrast dye and had a shorter fluoroscopy time, suggesting it may be more efficient in certain procedural aspects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Direct Comparison of Self-Expandable Portico Versus Balloon-Expandable Sapien 3 Devices for Transcatheter Aortic Valve Replacement: A Case-Matched Cohort Study. Mas-Peiro, S., Seppelt, PC., Weiler, H., et al.[2020]

Transcatheter aortic valve replacement (TAVR) is now a standard treatment for patients with severe aortic stenosis at intermediate risk for surgery, showcasing its growing acceptance in clinical practice.

The Evolut PRO system, a new self-expandable valve from Medtronic, represents significant advancements in TAVR technology, aimed at enhancing device quality and safety compared to earlier models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From CoreValve to Evolut PRO: Reviewing the Journey of Self-Expanding Transcatheter Aortic Valves. Mahtta, D., Elgendy, IY., Bavry, AA.[2023]

In a study of 1612 patients undergoing transcatheter aortic valve replacement (TAVR), the SAPIEN 3 Ultra valve showed higher device success rates (92.7%) compared to the Evolut valve (87.6%), indicating better overall performance.

The Evolut valve was associated with a higher need for permanent pacemaker implantation (15.2% vs. 8.4%) and more frequent moderate paravalvular leakage (3.7% vs. 1.3%) compared to the Ultra valve, although it had fewer cases of elevated gradients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter comparison of latest-generation balloon-expandable versus self-expanding transcatheter heart valves: Ultra versus Evolut. Rheude, T., Pellegrini, C., Allali, A., 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]

Citations

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

Real-World Outcomes for the Fifth-Generation Balloon ... S3UR TAVR is associated with lower mean gradients and lower rates of PVL than earlier generations of balloon expandable transcatheter heart valve platforms.

2. 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 ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.123.012873

Final 3-Year Outcomes of a Randomized Trial Comparing ... Early differences between NEO and S3 did not translate into significant differences in clinical outcomes or bioprosthetic valve failure throughout 3 years.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30501446/

Newer-generation of Edwards transcatheter aortic valve ... In this review, we summarize the available data on the SAPIEN-3 transcatheter heart valve system and we highlight the special features of the ...

5. 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.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40829754/

Safety and efficacy of transcatheter aortic valve ... The findings of this study demonstrate that BEVs implantation in patients with Sievers type 0 BAV is associated with favorable safety and ...