Edwards PASCAL System for Tricuspid Regurgitation

(CLASP II TR Trial)

Recruiting at 86 trial locations

Overseen By Edwards TMTT Clinical Affairs

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Disqualifiers: Heart failure, Coronary artery disease, Stroke, 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: 30

Duration: 12 months

870 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 the Edwards PASCAL System, a device designed to assist individuals with severe tricuspid regurgitation. This condition involves a leaking tricuspid valve, leading to symptoms like fatigue and swelling. The trial compares this new device with standard medical treatment to determine which is more effective. It is ideal for those who continue to experience symptoms or have been hospitalized due to tricuspid regurgitation, despite medication, and are unsuitable candidates for traditional surgery. As an unphased trial, it provides patients with access to innovative treatment options not yet widely available.

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 the Edwards PASCAL System is safe for tricuspid regurgitation?

Research has shown that the Edwards PASCAL System has promising safety results from earlier studies. One study found that after a year, patients treated with the PASCAL system experienced significant improvements with few risks. Common potential risks include heart problems such as heart attacks or strokes, but these are rare.

The PASCAL system has also treated mitral regurgitation and demonstrated a good safety record over three years. While still under study for tricuspid regurgitation, these findings provide some reassurance about its safety for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Edwards PASCAL System for tricuspid regurgitation because it offers a minimally invasive approach to valve repair. Unlike traditional surgical options which require open-heart surgery, this system is delivered via a catheter, reducing recovery time and potential complications. Most current treatments focus on managing symptoms with medications, but the PASCAL System directly targets the structural issue by repairing the valve itself. This innovative approach could provide significant improvements in patient outcomes and quality of life.

What evidence suggests that the Edwards PASCAL System is effective for tricuspid regurgitation?

Research has shown that the Edwards PASCAL System effectively treats tricuspid regurgitation, a heart valve problem. In this trial, some participants will receive transcatheter tricuspid valve repair with the Edwards PASCAL System alongside optimal medical therapy (OMT). One study found that patients experienced fewer complications and lived longer. Another study reported that patients felt better and could do more in their daily lives. These findings suggest that the PASCAL System could be a good option for people at high risk with regular surgery. ^{1 2 4 6 7}

Who Is on the Research Team?

Charles Davidson, MD

Principal Investigator

Northwestern University

Michael J. Mack, MD

Principal Investigator

Baylor Scott and White Health

Gorav Ailawadi, MD

Principal Investigator

University of Michigan

Martin B. Leon, MD

Principal Investigator

Columbia University

Allen Anderson, MD

Principal Investigator

UT Health San Antonio

Are You a Good Fit for This Trial?

This trial is for adults with severe tricuspid regurgitation, a heart valve disease causing symptoms or hospitalization despite medical treatment. Candidates must be at intermediate or higher risk for surgery complications as assessed by a Heart Team and willing to follow the study's procedures.

Inclusion Criteria

Patient is able and willing to give informed consent, follow protocol procedures, and comply with follow-up visit requirements

I have moderate to severe heart issues or was hospitalized for heart failure in the last year.

I have heart issues related to tricuspid regurgitation that aren't improving with current treatment.

Exclusion Criteria

I have not had a cardioversion procedure in the last 30 days.

I have not had carotid surgery in the last 30 days.

The structure of your tricuspid valve makes it impossible for the device to be placed and work correctly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcatheter tricuspid valve repair with the Edwards PASCAL system and optimal medical therapy

12 months

Visits at discharge, 30 days, 3 months, 6 months, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Annually through 5 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Edwards PASCAL System
• Optimal Medical Therapy

Trial Overview The Edwards PASCAL Transcatheter Valve Repair System is being tested against Optimal Medical Therapy in patients with symptomatic severe tricuspid regurgitation who are not good candidates for surgery due to high risk of mortality.

How Is the Trial Designed?

Group I: Single-Arm Registry Experimental Treatment 1 Intervention

Transcatheter tricuspid valve repair with the Edwards PASCAL System in conjunction with optimal medical therapy (OMT) in patients with tricuspid regurgitation who are not eligible for randomization

Group II: Edwards PASCAL System & OMT Experimental Treatment 1 Intervention

Transcatheter tricuspid valve repair with the Edwards PASCAL system in patients on optimal medical therapy (OMT) with tricuspid regurgitation

Group III: Continued Access Study Experimental Treatment 1 Intervention

Transcatheter tricuspid valve repair with the Edwards PASCAL system in patients on optimal medical therapy (OMT) with tricuspid regurgitation

Group IV: Optimal Medical Therapy (OMT) Active Control 1 Intervention

Optimal medical therapy (OMT) alone in patients with tricuspid regurgitation

Edwards PASCAL System is already approved in European Union, United States for the following indications:

Approved in European Union as PASCAL Precision Transcatheter Valve Repair System for:

• Mitral regurgitation
• Tricuspid regurgitation

Approved in United States as PASCAL Precision Transcatheter Valve Repair System for:

• Degenerative mitral regurgitation (DMR)

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

In a case involving an elderly female patient, local administration of recombinant factor VIIa (rFVIIa) effectively treated intractable hemorrhagic pericardial effusion after a TAVR procedure, demonstrating its potential as a targeted treatment option.

This approach showed no adverse effects or thromboembolic complications, suggesting that local rFVIIa administration may be safer and more effective than traditional methods like systemic rFVIIa, blood transfusions, or surgical re-exploration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-Pericardial Use of Recombinant Factor VIIa in a Patient With Acute Hemorrhagic Pericardial Effusion Following Transcutaneous Aortic Valve Replacement-A Case Report. Jaitly, V., Klein, K., Tint, H., et al.[2018]

The PASCAL transcatheter valve repair system was used in 18 patients with severe mitral regurgitation, resulting in significant reductions in the severity of the condition, with 22.2% achieving complete resolution (grade 0) and 61.1% showing mild improvement (grade I).

The procedure was safe, with no periprocedural complications reported, and the device's unique features allowed for tailored repairs based on individual patient anatomy, demonstrating its efficacy in treating severe mitral regurgitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitral valve leaflet repair with the new PASCAL system: early real-world data from a German multicentre experience. Kriechbaum, SD., Boeder, NF., Gaede, L., et al.[2021]

A 70-year-old man with severe tricuspid regurgitation successfully underwent transfemoral valve repair using the PASCAL system, which effectively reduced his condition.

The PASCAL device allowed for optimal leaflet insertion to address a significant coaptation gap without the need for ventilation maneuvers during the procedure, highlighting its efficacy and safety in complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Sedation in a Patient Undergoing Transfemoral Tricuspid Valve Repair Using the PASCAL System. Arikan, MX., Jorbenadze, R., Tavlaki, E., et al.[2021]

In a study involving 235 high-risk patients with severe tricuspid regurgitation (TR), the PASCAL and PASCAL Ace systems achieved a procedural success rate of 78%, effectively reducing TR to moderate or less in 78% of patients after treatment.

At a median follow-up of 173 days, the reduction in TR was sustained, and patients experienced significant improvements in symptoms, with 63% reporting better functional status, indicating both safety and efficacy of the PASCAL systems in treating TR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Experience With the Transcatheter Leaflet Repair System for Symptomatic Tricuspid Regurgitation. Wild, MG., Löw, K., Rosch, S., et al.[2022]

In a study of 17 patients undergoing cardiovascular surgery, the use of recombinant activated factor VII significantly reduced blood loss and improved coagulation test values, indicating its effectiveness in managing uncontrollable bleeding.

No adverse thromboembolic events were reported, highlighting the safety of recombinant activated factor VII when used appropriately in patients with normal platelet and fibrinogen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change of coagulation after NovoSeven® use for bleeding during cardiac surgery. Tomita, E., Takase, H., Tajima, K., et al.[2017]

The PASCAL Transcatheter Valve Repair System demonstrated a low major adverse event rate of 6.5% and an all-cause mortality rate of only 1.6% in 62 patients with severe mitral regurgitation, indicating its safety for use in this population.

At 30 days post-procedure, 98% of patients experienced a significant reduction in mitral regurgitation severity, and there were notable improvements in functional status and quality of life, as evidenced by increased walking distance and higher scores on quality of life assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study. Lim, DS., Kar, S., Spargias, K., et al.[2020]

A 72-year-old patient undergoing mitral valve replacement for infective endocarditis experienced severe bleeding post-surgery, which was effectively managed with recombinant activated factor VII (rFVIIa).

The patient's recovery was smooth after the intervention, leading to discharge on postoperative day 16, highlighting the potential efficacy of rFVIIa in managing intractable bleeding during cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa use in cardiac surgery--expanding the arsenal therapy for intractable bleeding? Kogan, A., Berman, M., Stein, M., et al.[2016]

In a systematic review of 16 cases of amniotic fluid embolism (AFE) patients treated with recombinant factor VIIa (rVIIa), outcomes were significantly worse compared to 28 AFE patients who did not receive rVIIa, with a risk ratio of 2.2 for death or permanent disability.

The study suggests that rVIIa should only be used in AFE patients when hemorrhage cannot be controlled by other means, such as massive blood component replacement, due to the increased risk of negative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of recombinant factor VIIa in patients with amniotic fluid embolism: a systematic review of case reports. Leighton, BL., Wall, MH., Lockhart, EM., et al.[2021]

The PASCAL transcatheter valve repair system demonstrated a high procedural success rate of 86% in 28 patients with severe tricuspid regurgitation, indicating its feasibility and safety for high-risk surgical patients.

At 30-day follow-up, 85% of patients had a significant reduction in tricuspid regurgitation severity, and there was a notable improvement in exercise capacity, with six-minute walk distances increasing from 240 m to 335 m.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate Use of the PASCAL Transcatheter Valve Repair System for Severe Tricuspid Regurgitation: A Multicenter, Observational, First-in-Human Experience. Fam, NP., Braun, D., von Bardeleben, RS., et al.[2020]

A 26-year-old man with osteogenesis imperfecta experienced significant bleeding during aortic valve replacement surgery, losing an average of 153 mL of blood per hour in the first 7 hours post-operation due to the fragility of his tissues.

The application of recombinant factor VIIa at a dose of 40 microg/kg successfully stopped the bleeding, demonstrating its efficacy in managing postoperative hemorrhage in patients with compromised tissue integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa after aortic valve replacement in a patient with osteogenesis imperfecta. Kastrup, M., von Heymann, C., Hotz, H., et al.[2019]

The Edwards PASCAL transcatheter valve repair system provides a new treatment option for patients with mitral and tricuspid regurgitation who cannot undergo surgery, allowing for personalized approaches based on individual anatomy.

Early evidence suggests that the PASCAL device has similar safety and efficacy to the Abbott MitraClip system, but further randomized studies and long-term data are necessary to validate these initial findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PASCAL Device-Early Experience with a Leaflet Approximation Device: What Are the Benefits/Limitations Compared with the MitraClip? Corpataux, N., Winkel, MG., Kassar, M., et al.[2021]

Citations

1. edwards.com edwards.com/healthcare-professionals/products-services/transcatheter-mitral-tricuspid-technologies/pascal-precision-system

The PASCAL Precision system Three-year outcomes for the transcatheter repair in patients with mitral regurgitation from the CLASP study. ... Edwards PASCAL Precision Transcatheter Valve ...

2. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf22/P220003D.pdf

Edwards PASCAL Precision Transcatheter Valve Repair ... Safety and effectiveness of the PASCAL Precision system has not been established in pediatric patients. 6.0 Potential Adverse Events. Below is a list of the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04614402

NCT04614402 | Transcatheter Repair of Tricuspid ... The objectives of this clinical study are to collect data on the safety and effectiveness of the PASCAL System and PASCAL Precision System in improving TR, ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.031881

One‐Year Outcomes According to Mitral Regurgitation ... This study reports 1-year outcomes of mitral valve transcatheter edge-to-edge repair with the PASCAL system according to MR etiology in a large all-comer ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37137586/

1-Year Outcomes of Transcatheter Tricuspid Valve Repair The PASCAL system demonstrated low complication and high survival rates, with significant and sustained improvements in TR, functional status, and quality of ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf22/P220003B.pdf

Summary of Safety and Effectiveness Data (SSED) The probable risks of the PASCAL Precision system include MAEs, such as cardiovascular death, stroke, myocardial infarction, new need for renal ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S193687982301381X

1-Year Outcomes of Transcatheter Edge-to-Edge Repair in ... At 1 year, treatment with the PASCAL system demonstrated safety and significant MR reduction, with continued improvement in clinical, echocardiographic, ...