TAVR for Aortic Stenosis

(PROGRESS Trial)

Recruiting at 80 trial locations

Overseen By Edwards THV Clinical Affairs

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Disqualifiers: Aortic regurgitation, LVEF < 20%, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 30 days

2250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new heart valve system for individuals with moderate aortic stenosis, a condition where the heart's aortic valve narrows, leading to symptoms or heart problems. Participants will receive the Edwards SAPIEN 3 valve through Transcatheter Aortic Valve Replacement (TAVR), a procedure that places the new valve without open-heart surgery. Some participants will be observed under clinical surveillance. Ideal candidates are those aged 65 or older with moderate aortic stenosis and related symptoms. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future treatments for aortic stenosis.

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 the Edwards SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve systems are safe for treating aortic stenosis?

Research has shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra heart valves are generally safe. Studies have found that mortality rates are low after receiving this treatment. Specifically, over five years, only 10% of those with the SAPIEN 3 valve died, compared to 8.2% who underwent traditional surgery. The risk of a serious stroke was also low, at just 2.9%.

These results suggest that the treatment is well-tolerated, with recipients reporting few serious issues. The FDA has approved the treatment for another use, further supporting its safety. However, as with any medical treatment, discussing potential risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Edwards SAPIEN 3 and SAPIEN 3 Ultra are unique because they offer a less invasive alternative to traditional open-heart surgery for treating aortic stenosis. Most current treatments involve surgical valve replacement, which requires opening the chest. In contrast, these devices are used in a procedure called Transcatheter Aortic Valve Replacement (TAVR), which involves inserting the new valve through a catheter, usually via a small incision in the leg. This method potentially reduces recovery time and offers an option for patients who are high-risk or unable to undergo open-heart surgery. Researchers are excited because TAVR could expand treatment options and improve outcomes for patients with aortic stenosis.

What evidence suggests that the Edwards SAPIEN 3 / SAPIEN 3 Ultra Transcatheter Heart Valve systems are effective for aortic stenosis?

Research has shown that the Edwards SAPIEN 3 and SAPIEN 3 Ultra heart valves effectively treat aortic stenosis, a condition where the heart's aortic valve narrows. Studies have found that these valves leak less and perform better than older versions. The SAPIEN 3 Ultra Resilia, in particular, improves heart function and reduces complications after the procedure. Most importantly, these valves provide significant relief for patients with severe aortic stenosis. This trial will evaluate the effectiveness of the Edwards SAPIEN 3 and SAPIEN 3 Ultra in treating moderate cases of aortic stenosis through Transcatheter Aortic Valve Replacement (TAVR), compared to Clinical Surveillance (CS). ^{3 5 6 7 8}

Who Is on the Research Team?

Raj Makkar

Principal Investigator

Cedars-Sinai Medical Center, Los Angeles, CA, USA

Jeroen J Bax, MD, PhD

Principal Investigator

Leiden University Medical Center, Leiden, The Netherlands

Philippe Généreux, MD

Principal Investigator

Morristown Medical Center, Morristown, NJ, USA

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older with moderate, calcific aortic stenosis who may have symptoms or signs of heart damage. They must understand the study and agree to participate. It's not for those with mechanical heart valves, severe valve leakage, very weak hearts (LVEF < 20%), certain types of aortic valves, high risk of artery blockage after TAVR, previous treatments for severe AS, unsuitable heart anatomy for the procedure, or evidence of intracardiac mass.

Inclusion Criteria

The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent.

I have been diagnosed with moderate aortic stenosis.

I am 65 years old or older.

Exclusion Criteria

My heart's structure increases my risk of artery blockage after a valve replacement.

My body's structure allows for safe placement of medical devices through the thigh.

I have severe leakage in my aortic valve.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either transcatheter aortic valve replacement (TAVR) or clinical surveillance

30 days

1 visit (in-person) for TAVR procedure, regular monitoring for clinical surveillance

Follow-up

Participants are monitored for safety and effectiveness, including primary and secondary endpoints

2 years

Regular follow-up visits (in-person and virtual)

Continued Access

Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial

What Are the Treatments Tested in This Trial?

Interventions

• Edwards SAPIEN 3/ SAPIEN 3 Ultra

Trial Overview The PROGRESS trial tests the safety and effectiveness of Edwards SAPIEN Transcatheter Heart Valve systems in treating moderate aortic stenosis. Participants will receive one of these valve systems through a less invasive method compared to traditional surgery.

How Is the Trial Designed?

Group I: TAVR Experimental Treatment 1 Intervention

Transcatheter Aortic Valve Replacement (TAVR)

Group II: CS Active Control 1 Intervention

Clinical Surveillance (CS)

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

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

• Severe aortic stenosis
• Replacement of failing mitral valve in patients who are too high risk for open-heart surgery when the valve has already been repaired with an artificial (prosthetic) ring
• Replacement of failing previously implanted surgical biological aortic or mitral valve, or transcatheter aortic valve in patients who are too high risk for open-heart surgery

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

• Severe aortic stenosis
• Symptomatic heart disease due to severe native aortic valve stenosis

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

Transcatheter aortic valve replacement (TAVR) using the SAPIEN 3 valve is safe and effective for Japanese dialysis patients with severe aortic stenosis, showing a low in-hospital mortality rate of 3.6% and a 1-year survival rate of 89.3%.

Patients experienced significant improvements in heart function and quality of life measures after the procedure, with no cases of structural valve deterioration during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year outcomes of the pivotal clinical trial of a balloon-expandable transcatheter aortic valve implantation in Japanese dialysis patients. Maeda, K., Kuratani, T., Mizote, I., et al.[2022]

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]

The transcarotid (TC) approach for transcatheter aortic valve replacement (TAVR) using the Edwards Sapien 3 device demonstrated a high procedural success rate of 97% in a study of 314 patients, suggesting it is a viable alternative for those ineligible for transfemoral access.

At 30 days post-procedure, TC-TAVR showed a 3.2% mortality rate and low rates of major complications, including 4.1% major bleeding and 1.6% stroke, indicating that it is a safe option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcarotid Approach for Transcatheter Aortic Valve Replacement With the Sapien 3 Prosthesis: A Multicenter French Registry. Overtchouk, P., Folliguet, T., Pinaud, F., et al.[2020]

The SAPIEN 3 transcatheter heart valve system has shown improved safety and efficacy in low-risk patients undergoing TAVR, particularly with better positioning and reduced rates of paravalvular leakage compared to earlier models.

Despite its advantages, there are concerns about higher rates of conduction disturbances and uncertainties regarding long-term valve performance, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device profile of the SAPIEN 3 transcatheter heart valve in low-risk patients with aortic stenosis: overview of its safety and efficacy. Alperi, A., Mesnier, J., Panagides, V., et al.[2022]

The third generation Sapien 3 device for TAVR showed excellent outcomes, with 92.2% of patients experiencing none or trace paravalvular regurgitation, indicating its efficacy in reducing this complication.

While major vascular complications and bleeding were rare, the study noted a 25.5% rate of permanent pacemaker implantation, suggesting a need for further investigation into this issue in larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome. Murray, MI., Geis, N., Pleger, ST., et al.[2018]

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 1,078 patients with severe aortic stenosis, transcatheter aortic valve replacement (TAVR) using the SAPIEN 3 valve significantly improved quality of life (QoL) at both 1 month and 1 year compared to previous-generation TAVR devices and surgical aortic valve replacement (SAVR).

At 1 month, patients receiving S3-TAVR reported a QoL improvement of 15.6 points compared to SAVR and 3.7 points compared to XT-TAVR, with these differences remaining statistically significant at 1 year, indicating sustained benefits of the SAPIEN 3 valve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of SAPIEN 3 Transcatheter Valve Implantation on Health Status in Patients With Severe Aortic Stenosis at Intermediate Surgical Risk: Results From the PARTNER S3i Trial. Baron, SJ., Thourani, VH., Kodali, S., et al.[2020]

The SAPIEN 3 Ultra (S3-Ultra) system significantly reduced the incidence of ≥mild paravalvular leakage (PVL) compared to the SAPIEN 3 (S3) system, with rates of 7.2% versus 22.3%, indicating improved efficacy in valve performance.

Patients receiving the S3-Ultra also experienced a lower incidence of major vascular complications (4.5% vs. 11.4%), suggesting that the S3-Ultra may offer comparable safety benefits alongside its improved hemodynamic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic comparison of transcatheter aortic valve replacement with the SAPIEN 3 Ultra versus SAPIEN 3: The HomoSAPIEN registry. Moriyama, N., Lehtola, H., Miyashita, H., et al.[2021]

In a study of 235 patients with severe aortic stenosis, the use of the Edwards Sapien 3 valve for transcatheter aortic valve implantation (TAVI) resulted in no cases of moderate or severe residual aortic regurgitation, indicating high device success.

The procedure, performed without general anesthesia, showed low rates of major vascular complications (3.0%), mortality (2.6%), and stroke (2.1%) within 30 days, demonstrating its safety and efficacy across different valve sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience. Wöhrle, J., Gonska, B., Rodewald, C., et al.[2019]

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]

In a study of 85 patients undergoing TAVR with the SAPIEN 3 valve, nonagenarians (aged 90 and above) experienced similar early mortality rates compared to younger patients, indicating that TAVR is a viable option for elderly patients with severe aortic stenosis.

However, nonagenarians had a higher incidence of life-threatening bleeding and major vascular complications (11.8% vs. 1.5% in younger patients), suggesting that while TAVR is safe, older patients may face greater procedural risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians. Ichimoto, E., Arnofsky, A., Wilderman, M., et al.[2022]

Citations

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

Real-World Outcomes for the Fifth-Generation Balloon ... The SAPIEN 3 Ultra Resilia (S3UR) valve is a fifth-generation device and represents the latest iteration of balloon-expandable THV technology.

2. eurointervention.pcronline.com eurointervention.pcronline.com/article/performance-and-outcomes-of-the-sapien-3-ultra-resilia-transcatheter-heart-valve-in-the-ocean-tavi-registry

Performance and outcomes of the SAPIEN 3 Ultra RESILIA ... CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance.

3. 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.

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf14/P140031S162B.pdf

Summary of Safety and Effectiveness Data (SSED) 1) The Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN 3 Ultra RESILIA Transcatheter. Heart Valve system is indicated for relief of aortic stenosis in patients ...

5. tctmd.com tctmd.com/news/better-1-year-echo-and-clinical-outcomes-new-sapien-ultra-resilia

Better 1-Year Echo and Clinical Outcomes With New ... The latest-generation balloon-expandable Sapien 3 Ultra Resilia were significantly better in a range of patients with severe aortic stenosis, including those ...

6. 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 ...

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

Transcatheter SAPIEN 3 Ultra RESILIA Low rates of all-cause mortality through five years (10.0% SAPIEN 3 TAVR vs. 8.2% with SAVR). Low rates of disabling stroke through five years (2.9% SAPIEN 3 ...

8. treatheartvalvefailure.com treatheartvalvefailure.com/important-risk-information

Important Risk Information | Heart Valve Failure Patient View Important Risk Information for Edwards SAPIEN 3, SAPIEN 3 Ultra and SAPIEN 3 Ultra RESILIA. See full Prescribing and Safety Information.