Aortic Valve Replacement for Aortic Stenosis

(SMART Trial)

Not currently recruiting at 98 trial locations

Overseen By SMART Trial Clinical Study Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medtronic Cardiovascular

Disqualifiers: Multivessel coronary disease, Pregnancy, Previous valve replacement, others

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

Compensation: Varies

Number of Visits: 31

Duration: Immediate post-procedure to discharge

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two types of heart valve replacements for individuals with severe aortic stenosis, a condition where the heart's aortic valve becomes too narrow. The trial aims to assess the safety and effectiveness of these valves when inserted through a catheter, avoiding open-heart surgery. It compares self-expanding valves (such as the Medtronic Evolut PRO, Evolut PRO+, or Evolut FX TAV Systems) to balloon-expandable ones (like the Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems). A small part of the study evaluates how well these valves perform during exercise. Suitable candidates have been advised they need a valve replacement and experience severe symptoms due to the narrowed valve. As an unphased trial, this study provides patients the chance 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 team or your doctor.

What prior data suggests that these transcatheter aortic valve replacement systems are safe?

Studies have shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra heart valve systems are generally well-tolerated. For example, one study found a low rate of strokes and other brain blood flow issues at just 1.9%. Other research confirms these systems are safe for patients with severe narrowing of the heart's aortic valve.

Research into the Medtronic Evolut PRO and Evolut PRO+ valve systems also supports their safety. One study highlighted that the Evolut valves performed well over five years, with no major safety concerns. Another report on the Evolut systems in adults found no new safety issues.

These findings suggest that both the Edwards and Medtronic systems are generally safe for adults needing aortic valve replacement, with a low risk of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for aortic stenosis because they offer innovative approaches to replacing the aortic valve without traditional open-heart surgery. The Edwards SAPIEN 3 and SAPIEN 3 Ultra systems use a balloon-expandable valve, which allows for precise placement and potentially better patient outcomes. Meanwhile, the Medtronic Evolut PRO, PRO+, and FX systems are self-expanding, which can adapt to the patient's anatomy more naturally and reduce the risk of complications. These minimally invasive transcatheter aortic valve replacement (TAVR) systems aim to improve recovery times and expand treatment options for patients who might not be candidates for surgery.

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

Research has shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra systems, which participants in this trial may receive, effectively treat severe aortic stenosis, a condition where the aortic valve narrows. Studies have found these systems to be both effective and affordable. Specifically, 87% of patients experienced little to no leakage around the valve 30 days after treatment.

Similarly, the Medtronic Evolut PRO, Evolut PRO+, and Evolut FX systems, another treatment option in this trial, also effectively address this condition. The SMART Trial reported positive outcomes, including low rates of permanent pacemaker implantation, which is encouraging. Both systems aim to improve blood flow through the heart in patients with aortic stenosis. ^{1 3 6 7 8}

Who Is on the Research Team?

Didier Tchétché, MD

Principal Investigator

Clinique Pasteur Toulouse, France

Howard Herrmann, MD

Principal Investigator

University of Pennsylvania, United States

Roxana Mehran, MD

Principal Investigator

Mount Sinai School of Medicine, United States

Are You a Good Fit for This Trial?

This trial is for adults with severe aortic stenosis and a small aortic annulus who are candidates for valve replacement via TAVR. Participants must be able to attend follow-up visits, have less than 15% risk of mortality from the procedure, suitable anatomy for both Medtronic Evolut and Edwards SAPIEN systems, and access through the femoral artery.

Inclusion Criteria

I have been diagnosed with severe aortic stenosis through an echocardiogram.

My body is fit for a heart valve procedure through my leg.

Your doctors think the risk of serious complications during surgery is less than 15%.

Exclusion Criteria

I currently have COVID-19 or have had it before.

I have severe heart artery disease or issues with my heart's main artery.

I am under the legal age or unable to give consent due to legal or mental reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAVR with either a Medtronic SE TAV or an Edwards BE THV

Immediate post-procedure to discharge

Pre-procedure, post-procedure, and at discharge

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

30 days, 12 months, and annually until 5 years

Stress Echocardiography Sub-study

Performance of SE versus BE TAVR evaluated during exercise stress echocardiographic testing

Conducted at 12-month visit

1 visit (in-person) at select sites

What Are the Treatments Tested in This Trial?

Interventions

• Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
• Medtronic Evolut PRO, Evolut PRO+ or Evolut FX TAV Systems
• Medtronic Evolut PRO or Evolut PRO+ TAV Systems

Trial Overview The trial compares two types of heart valve systems: self-expanding (Medtronic Evolut PRO/PRO+/FX) versus balloon-expandable (Edwards SAPIEN 3/3 Ultra) in patients needing transcatheter aortic valve replacement. It includes an exercise stress echocardiography sub-study at some locations.

How Is the Trial Designed?

Group I: Medtronic Self-Expanding TAV Experimental Treatment 1 Intervention

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Group II: Edwards Balloon-Expandable THV Experimental Treatment 1 Intervention

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Who Is Running the Clinical Trial?

Medtronic Cardiovascular

Lead Sponsor

Trials

78

Recruited

37,300+

Geoff Martha

Medtronic Cardiovascular

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Kendra J. Grubb

Medtronic Cardiovascular

Chief Medical Officer

MD from Emory University

Published Research Related to This Trial

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 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 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 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 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]

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]

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]

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]

Citations

1. 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 ...

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

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 transcatheter aortic ...

3. 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) ...

4. 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 ...

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

Transcatheter SAPIEN 3 Ultra A prospective multi center study of the SAPIEN 3 Ultra system in intermediate-risk patients with severe aortic stenosis. Presented at: PCR London Valves 2019; ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6171512/

Spotlight on the SAPIEN 3 transcatheter heart valve - PMC With the S3 THV, the rate of CVE has been comparatively low (1.9%).22 This reduced rate of CVE with the S3 THV in line with a general decrease ...