Aortic Valve-in-Valve for Aortic Stenosis

(P3-AVIV Trial)

Recruiting at 30 trial locations

Overseen by Mayra Guerrero, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Edwards Lifesciences

Disqualifiers: Severe regurgitation, Myocardial infarction, Stroke, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will assess the safety and effectiveness of the SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve (THV) in patients with a failing aortic bioprosthetic valve.

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 data supports the idea that Aortic Valve-in-Valve for Aortic Stenosis is an effective treatment?

The available research shows that the SAPIEN 3 and SAPIEN 3 Ultra valves are effective treatments for aortic stenosis. Studies have shown that these valves have low rates of complications, such as vascular injuries and leaks around the valve. They also have lower rates of stroke and death compared to traditional surgical valve replacement, especially in patients who are at intermediate or high risk for surgery. This suggests that the SAPIEN 3 and SAPIEN 3 Ultra valves are not only effective but also safer alternatives for many patients. ^{1 2 3 4 5}

What safety data is available for the Aortic Valve-in-Valve treatment using the SAPIEN 3 valve?

The SAPIEN 3 valve has been evaluated in several studies for its safety and efficacy. The FDA approved the Edwards SAPIEN transcatheter heart valve based on the PARTNER trial, which showed it to be noninferior to surgical aortic valve replacement in high-risk patients. The SAPIEN 3 valve has demonstrated good 30-day clinical outcomes in intermediate-risk patients and has been compared favorably to surgical valve replacement. Additionally, the SAPIEN 3 valve incorporates features to reduce aortic regurgitation and vascular complications, as shown in comparisons with the Sapien XT valve system. ^{2 6 7 8 9}

Is the Edwards SAPIEN 3/SAPIEN 3 Ultra THV treatment a promising option for aortic stenosis?

Yes, the Edwards SAPIEN 3/SAPIEN 3 Ultra THV treatment is promising for aortic stenosis. It is a newer version of a heart valve replacement that can be done without open-heart surgery. This treatment has shown low rates of complications like stroke and death, and it helps reduce leaks around the valve. It is especially beneficial for patients who are at higher risk for traditional surgery. ^{1 2 3 4 10}

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

Eligibility Criteria

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

Your heart imaging shows a mass, blood clot, or infection.

Trial Timeline

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

Treatment Details

Interventions

• Edwards SAPIEN 3/SAPIEN 3 Ultra THV (Transcatheter Heart Valve)
• Edwards SAPIEN 3 THV (Transcatheter Heart Valve)

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.

Participant Groups

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).

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

Findings from Research

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 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]

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]

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 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]

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]

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 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]

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]

References

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

Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves: Comparison of SAPIEN 3 Ultra Versus SAPIEN 3. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards SAPIEN 3 Transcatheter Valve For Aortic Stenosis. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Next-generation balloon-expandable transcatheter heart valve: the SAPIEN 3 Ultra valve. [2022]

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

Reframing Optimal Implantation of the Sapien 3 Transcatheter Heart Valve. [2022]

6. United States 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. [2013]

7. United States 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. [2016]

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

Transaortic transcatheter aortic valve implantation: experience from the Kiel study. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve. [2014]

10. Germany 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. [2017]