TAVR for Aortic Stenosis

(PROGRESS Trial)

Recruiting at 77 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

Trial Summary

What is the purpose of this trial?

This trial tests advanced heart valves that can be inserted without open-heart surgery in patients with a narrowed and stiff aortic valve due to calcium buildup. The new valve is placed through a small cut and guided to the heart, where it replaces the damaged valve. This minimally invasive procedure has recently become the only lifesaving solution for patients who cannot tolerate standard surgical valve replacement.

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 data supports the effectiveness of the treatment Edwards SAPIEN 3/ SAPIEN 3 Ultra, Edwards SAPIEN 3, SAPIEN 3 Ultra, SAPIEN 3 Ultra RESILIA for aortic stenosis?

Research shows that the SAPIEN 3 valve used in transcatheter aortic valve replacement (TAVR) provides good short-term and long-term outcomes for patients with severe aortic stenosis, especially those at intermediate surgical risk. It has been designed to reduce complications and improve quality of life compared to older devices and surgical options. ^{1 2 3 4 5}

Is TAVR with the SAPIEN 3 valve safe for humans?

TAVR with the SAPIEN 3 valve has shown good short-term safety outcomes in patients with severe aortic stenosis, especially those at high surgical risk. The FDA has approved it for high-risk patients, indicating that its benefits outweigh the risks compared to traditional surgery. ^{1 2 6 7 8}

What makes the SAPIEN 3/SAPIEN 3 Ultra treatment unique for aortic stenosis?

The SAPIEN 3 and SAPIEN 3 Ultra are unique because they are balloon-expandable valves used in transcatheter aortic valve replacement (TAVR), which is less invasive than traditional surgery and suitable for patients at various risk levels, including those who are elderly or have other health conditions that make surgery risky. These valves are designed to reduce complications like paravalvular regurgitation (leakage around the valve) and issues at the site where the valve is inserted. ^{1 2 9 10 11}

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

Eligibility Criteria

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.

You have a mechanical or bioprosthetic aortic valve already in place.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome. [2018]

3. United States 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. [2019]

4. United States 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. [2020]

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

Transcarotid Approach for Transcatheter Aortic Valve Replacement With the Sapien 3 Prosthesis: A Multicenter French Registry. [2020]

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

Hemodynamic comparison of transcatheter aortic valve replacement with the SAPIEN 3 Ultra versus SAPIEN 3: The HomoSAPIEN registry. [2021]

7. 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]

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

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

9. China pubmed.ncbi.nlm.nih.gov

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians. [2022]

10. England 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. [2022]

11. Netherlands 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. [2022]