Edwards PASCAL System for Tricuspid Regurgitation

(CLASP II TR Trial)

Recruiting at83 trial locations

Overseen by Charles Davidson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Edwards Lifesciences

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

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new device that fixes a leaky heart valve without surgery in patients who are too risky for traditional surgery. The device helps the valve close properly to stop blood from leaking backward. The first device specifically designed for this purpose is the paravalvular leak device (PLD - Occlutech).

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 data supports the effectiveness of the Edwards PASCAL System treatment for tricuspid regurgitation?

The PASCAL System has shown success in reducing tricuspid regurgitation in a patient with severe symptoms, and it has been used effectively for mitral regurgitation, suggesting potential benefits for tricuspid valve repair as well. ^{1 2 3 4 5}

Is the Edwards PASCAL System safe for humans?

The Edwards PASCAL System has been used in studies for heart valve repair, showing it is generally safe for humans. In a study for severe tricuspid regurgitation, it was successfully used without major safety concerns, and early results from other studies also support its safety. ^{1 3 4 5 6}

How is the Edwards PASCAL System treatment for tricuspid regurgitation different from other treatments?

The Edwards PASCAL System is unique because it is a transcatheter valve repair system specifically designed for treating tricuspid regurgitation, offering a minimally invasive alternative to open-heart surgery. This system allows for precise repair of the valve without the need for major surgery, which can be beneficial for patients who are at high risk for surgical complications. ^{7 8 9 10 11}

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

Eligibility Criteria

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 am 18 years old or older.

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

Exclusion Criteria

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• Edwards PASCAL System (Transcatheter Valve Repair System)
• Optimal Medical Therapy (Other)

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.

Participant Groups

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

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study. [2020]

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

Multicenter Experience With the Transcatheter Leaflet Repair System for Symptomatic Tricuspid Regurgitation. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Mitral valve leaflet repair with the new PASCAL system: early real-world data from a German multicentre experience. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Deep Sedation in a Patient Undergoing Transfemoral Tricuspid Valve Repair Using the PASCAL System. [2021]

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

The PASCAL Device-Early Experience with a Leaflet Approximation Device: What Are the Benefits/Limitations Compared with the MitraClip? [2021]

6. United States 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. [2020]

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

Use of recombinant factor VIIa in patients with amniotic fluid embolism: a systematic review of case reports. [2021]

8. England 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. [2018]

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

Change of coagulation after NovoSeven® use for bleeding during cardiac surgery. [2017]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa after aortic valve replacement in a patient with osteogenesis imperfecta. [2019]

11. Italy pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa use in cardiac surgery--expanding the arsenal therapy for intractable bleeding? [2016]