Aortic Valve-in-Valve for Aortic Stenosis

(P3-AVIV Trial)

Recruiting at 31 trial locations

Overseen By Edwards THV Clinical Affairs

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Disqualifiers: Severe regurgitation, Myocardial infarction, Stroke, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new heart valve treatment for individuals with a failing aortic valve. It focuses on the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve to assist those whose previous valve replacements no longer function effectively. The trial seeks participants with moderate or severe narrowing or leaking of their heart valve and symptoms affecting daily life, such as difficulty breathing or fatigue during regular activities. As an unphased study, this trial provides a unique opportunity to advance heart valve treatment options.

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

The trial protocol does not specify if you need to stop your current medications. However, you must be able to tolerate antithrombotic/anticoagulation therapy during or after the valve implant procedure.

What prior data suggests that the SAPIEN 3/SAPIEN 3 Ultra THV is safe for patients with a failing aortic bioprosthetic valve?

Research shows that the Edwards SAPIEN 3 and SAPIEN 3 Ultra heart valves are generally well-accepted by patients. Studies have demonstrated that these valves can be safely used in people with severe aortic stenosis, a narrowing of the heart valve opening. One study found that the SAPIEN 3 Ultra valve resulted in fewer leaks around the valve without increasing the risk of death. Additionally, the FDA has approved these valves for treating certain heart conditions, indicating they have passed safety checks for those uses. Overall, evidence supports their safety in humans for similar heart issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Edwards SAPIEN 3 and SAPIEN 3 Ultra transcatheter heart valves because they offer a minimally invasive option for patients with a failing aortic bioprosthetic valve. Unlike traditional surgical valve replacement, which requires open-heart surgery, these transcatheter valves can be delivered through a catheter, reducing recovery time and surgical risk. This is particularly beneficial for patients who are not ideal candidates for another open-heart surgery. The innovative design of these valves allows for precise placement and improved hemodynamic performance, potentially leading to better outcomes for patients with aortic stenosis.

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

Research shows that the Edwards SAPIEN 3 and SAPIEN 3 Ultra heart valves effectively treat aortic stenosis, a condition where the heart's aortic valve narrows. In this trial, participants with a failing surgical or transcatheter bioprosthetic valve will undergo transcatheter aortic valve replacement (TAVR) using these valves. Studies have found very few complications within 30 days after the procedure. For instance, one study discovered that new cases of atrial fibrillation (a type of irregular heartbeat) were much lower with the SAPIEN 3 compared to traditional surgery. This treatment has also been linked to good results in different groups of patients, including those with complex heart issues. Overall, these findings suggest that the SAPIEN 3 valves are effective and safe for patients who need valve replacement. ^{1 2 6 7 8}

Who Is on the Research Team?

Alan Zajarias, MD

Principal Investigator

Washington University School of Medicine

Mayra Guerrero, MD

Principal Investigator

Mayo Clinic

Chris S Malaisrie, MD

Principal Investigator

Northwestern University Feinberg School of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with a failing aortic bioprosthetic valve showing significant stenosis or insufficiency. Candidates should have an internal diameter of their current valve between 18.5 and 28.5 mm, be in NYHA Functional Class II or higher, and considered low to intermediate surgical risk by the Heart Team.

Inclusion Criteria

My heart valve replacement is not working well, showing significant narrowing or leakage.

My heart valve replacement is between 18.5 mm and 28.5 mm in size.

My heart valve replacement is not working properly.

Exclusion Criteria

I haven't needed heart or lung support machines in the last 30 days.

Currently participating in an investigational drug or another device study

I have a thickened heart muscle that obstructs blood flow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo transcatheter aortic valve replacement (TAVR) with SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments like the Six-Minute Walk Test and KCCQ

30 days

2 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term outcomes such as all-cause mortality and stroke

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Edwards SAPIEN 3/SAPIEN 3 Ultra THV
• Edwards SAPIEN 3 THV

Trial Overview The PARTNER 3 Trial tests the safety and effectiveness of the SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve (THV) as a replacement for failing bioprosthetic valves in the aortic position.

How Is the Trial Designed?

Group I: TAVR - Failing surgical or transcatheter valve Experimental Treatment 1 Intervention

Patients with a failing surgical or transcatheter bioprosthetic valve will undergo transcatheter aortic valve replacement (TAVR).

Edwards SAPIEN 3/SAPIEN 3 Ultra THV is already approved in United States, European Union for the following indications:

Approved in United States as Edwards SAPIEN 3/SAPIEN 3 Ultra THV for:

• Severe aortic stenosis
• Failing (stenosed, insufficient, or combined) surgical or transcatheter bioprosthetic aortic valve
• Failing (stenosed, insufficient, or combined) surgical bioprosthetic mitral valve

Approved in European Union as Edwards SAPIEN 3/SAPIEN 3 Ultra THV for:

• Severe aortic stenosis
• Failing (stenosed, insufficient, or combined) surgical or transcatheter bioprosthetic aortic valve
• Failing (stenosed, insufficient, or combined) surgical bioprosthetic mitral valve

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 SAPIEN 3 Ultra transcatheter heart valve features a 40% taller external skirt compared to the previous SAPIEN 3 valve, which may enhance its performance and stability during implantation.

The delivery system for the SAPIEN 3 Ultra remains the same as the S3, ensuring proven deliverability and maintaining low rates of vascular complications, which is crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation balloon-expandable transcatheter heart valve: the SAPIEN 3 Ultra valve. Chatfield, A., Sathananthan, J., Wood, DA., et al.[2022]

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 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 study of 279 patients receiving the Sapien 3 transcatheter heart valve, those with higher implantation positions had significantly lower rates of in-hospital left bundle-branch block (LBBB), indicating better conduction outcomes.

While the implantation zone did not significantly affect the rate of permanent pacemaker implantation or overall mortality at 1 year, positioning the valve higher was associated with fewer conduction abnormalities, suggesting optimal placement may enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reframing Optimal Implantation of the Sapien 3 Transcatheter Heart Valve. Mailey, JA., Brennan, PF., Kearney, A., et al.[2022]

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 99 patients with severe aortic stenosis undergoing transaortic transcatheter aortic valve implantation (TAVI), both the SAPIEN-XT and SAPIEN-3 valves showed high procedural success and low complication rates, making them effective options for treatment.

The SAPIEN-3 valve demonstrated advantages over the SAPIEN-XT, including shorter fluoroscopy time and a lower need for post-operative dilatation, while both valves had comparable 30-day mortality rates of around 5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transaortic transcatheter aortic valve implantation: experience from the Kiel study. Petzina, R., Lutter, G., Wolf, C., et al.[2018]

The Edwards Sapien 3 transcatheter heart valve (THV) was successfully used in six valve-in-valve (ViV) procedures across aortic, mitral, and tricuspid positions, with no complications reported, indicating its safety and reliability for this application.

The design features of the Sapien 3, including the polyethylene terephthalate cuff for better sealing, resulted in no paravalvular leakage or elevated transvalvular gradients, even in cases where the THV was slightly undersized compared to the original bioprosthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valve-in-Valve Procedures in Failing Biological Xenografts Using a Novel Balloon-Expandable Device: Experience in Aortic, Mitral, and Tricuspid Positions. Schaefer, A., Conradi, L., Seiffert, M., et al.[2017]

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]

The Sapien 3 transcatheter heart valve (S3-THV) significantly reduced the incidence of at least mild aortic regurgitation (15.9% vs. 46.2%) compared to the previous Sapien XT valve (SXT-THV), indicating improved valve performance.

The S3-THV also showed enhanced safety with no major bleeding or vascular complications reported, while maintaining similar rates of pacemaker implantation and 30-day mortality compared to the SXT-THV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation with the new balloon-expandable Sapien 3 versus Sapien XT valve system: a propensity score-matched single-center comparison. Nijhoff, F., Abawi, M., Agostoni, P., et al.[2016]

The Edwards SAPIEN transcatheter heart valve (THV) system offers a less invasive treatment option for severe aortic stenosis, particularly for patients who are inoperable or at high surgical risk, as demonstrated in the pivotal PARTNER trial.

The development of successive models, the XT and S3, aims to enhance procedural outcomes, indicating ongoing improvements in the safety and efficacy of transcatheter heart valve technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve. Minha, S., Waksman, R.[2014]

Citations

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

Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN ... The Edwards SAPIEN 3 Ultra RESILIA transcatheter heart valve is comprised of a balloon-expandable, radiopaque, cobalt-chromium frame, trileaflet RESILIA bovine ...

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

Transcatheter SAPIEN 3 Ultra Limited clinical data are available for transcatheter aortic valve replacement in patients with a congenital bicuspid aortic valve who are deemed to be at low ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10293831/

The first clinical data of the SAPIEN 3 aortic valve in ... Taken together, our study confirms that the SAPIEN 3 valve has displayed excellent clinical results in the treatment of Chinese patients with AS ...

4. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.116.022797

One-Year Clinical Outcomes With SAPIEN 3 Transcatheter ... A recent report of the 30-day outcomes with the low-profile SAPIEN 3 transcatheter aortic valve replacement system demonstrated very low rates of adverse ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2023.04.049

Outcomes of SAPIEN 3 Transcatheter Aortic Valve ... At 1 year, rates of new atrial fibrillation were 6.1% following S3 TAVR and 30.1% following SAVR (P < 0.0001), with the majority occurring ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01808287

Safety and Performance Study of the Edwards SAPIEN 3 ... The purpose of this study is to assess the safety and device success of the Edwards SAPIEN 3 Transcatheter Heart Valve (S3 THV) and the Edwards Commander and ...

7. 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) ...

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, ...