Transcatheter Valve Repair for Mitral Regurgitation

(CLASP IID/IIF Trial)

Recruiting at 94 trial locations

Overseen By Wally Omar, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Must be taking: Heart failure medications

Disqualifiers: Stroke, Severe COPD, Pregnancy, 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: 31

Duration: Immediate procedure

1247 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial tests the safety and effectiveness of the Edwards PASCAL Transcatheter Valve Repair System for individuals with mitral valve issues that surgery cannot fix. It focuses on two types of mitral regurgitation: degenerative (DMR) and functional (FMR). The study compares the Edwards PASCAL System with the Abbott Mitraclip System. Ideal candidates have significant mitral valve leakage confirmed by an echo test and have been advised against surgery. Those with ongoing heart issues affecting daily life and who are on stable heart medications might be suitable participants. As an unphased trial, this study offers a unique opportunity to contribute to medical research and potentially benefit from cutting-edge treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are in the CLASP IIF cohort, you must be on stable heart failure medications.

What prior data suggests that the Edwards PASCAL Transcatheter Valve Repair System is safe for mitral regurgitation?

Research has shown that the Edwards PASCAL Transcatheter Valve Repair System is generally safe for individuals with mitral regurgitation, a condition where the heart's mitral valve doesn't close properly. One study found that a year after using the PASCAL system, patients experienced significant improvements, and the treatment was well-tolerated. However, like any medical procedure, potential risks exist. Reported side effects include heart-related death, stroke, and heart attack. Despite these risks, the treatment has demonstrated promising safety results, making it a viable option for those unable to undergo traditional surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Edwards PASCAL System for mitral regurgitation because it offers a new approach to heart valve repair. Unlike traditional surgical methods or the current Mitraclip system, the PASCAL device uses a unique transcatheter delivery system that can be less invasive, making it suitable for patients with complex anatomical features. This system is designed to be flexible and precise, potentially improving outcomes for patients who aren't ideal candidates for existing treatments. With its innovative clasping mechanism, the PASCAL system might offer better control and adaptability during procedures, which could lead to more effective and safer repairs of the mitral valve.

What evidence suggests that this trial's treatments could be effective for mitral regurgitation?

Research has shown that the Edwards PASCAL System, one of the treatments studied in this trial, effectively treats mitral regurgitation, a condition where the heart's mitral valve doesn't close properly. One study found that patients experienced significant improvement in symptoms and heart function within a year of using the PASCAL System. Another study demonstrated that these benefits lasted for up to three years. The system repairs the mitral valve through a minimally invasive procedure, ideal for individuals at high risk for traditional surgery. Overall, evidence supports its safety and effectiveness in reducing symptoms of mitral regurgitation. Participants in this trial may receive either the Edwards PASCAL System or the Abbott Mitraclip System, another treatment option under investigation. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert L. Smith, MD

Principal Investigator

The Heart Hospital Baylor Plano

Brian Whisenant, MD

Principal Investigator

Intermountain Medical Center

Scott Lim, MD

Principal Investigator

University of Virginia

Vinod Thourani, MD

Principal Investigator

Piedmont Healthcare

Linda Gillam, MD

Principal Investigator

Morristown Medical Center

Ralph Stephan von Bardeleben, MD

Principal Investigator

/ Universitätsmedizin Mainz- Zentrum für Kardiologie

Paul Grayburn, MD

Principal Investigator

The Heart Hospital Baylor Plano

Jörg Hausleiter, MD

Principal Investigator

LMU München, Campus Gorsshadern

Are You a Good Fit for This Trial?

This trial is for adults with severe mitral valve regurgitation who are at high risk for surgery. Candidates must be on stable heart medications, able to consent and comply with follow-up visits, have suitable valve morphology, and not be pregnant. Exclusions include prior mitral procedures (except some repairs), significant untreated coronary disease, recent stroke or DVT/PE, severe lung disease, or life expectancy under 12 months.

Inclusion Criteria

My heart valve and its function are suitable for the study.

Your heart's pumping ability is between 20% and 50%.

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

Exclusion Criteria

Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator

Patient is currently participating in another investigational biologic, drug or device clinical study where the primary study endpoint was not reached at time of enrollment

I am not pregnant nor planning to become pregnant in the next year, and I agree to use contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Transcatheter mitral valve repair with the Edwards PASCAL or Abbott MitraClip System

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Visits at discharge, 30 days, 6 months, and annually through 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abbott Mitraclip System
• Edwards PASCAL System

Trial Overview The trial tests the Edwards PASCAL Transcatheter Valve Repair System against the Abbott MitraClip System in patients with degenerative or functional mitral regurgitation deemed too risky for surgery. It aims to establish safety and effectiveness of these minimally invasive heart valve repair options.

How Is the Trial Designed?

Group I: Edwards PASCAL System - Single-Arm Registry Experimental Treatment 1 Intervention

Transcatheter mitral valve repair with the Edwards PASCAL System in patients with mitral regurgitation who were deemed non-randomizable by a central screening committee (CSC) due to complex anatomical features described in the current MitraClip Instructions for Use (IFU) but were considered suitable for the PASCAL system.

Group II: Edwards PASCAL System - CLASP IIF Experimental Treatment 1 Intervention

Transcatheter mitral valve repair with the Edwards PASCAL System in patients on guideline directed medical therapy with functional mitral regurgitation

Group III: Edwards PASCAL System - CLASP IID Experimental Treatment 1 Intervention

Transcatheter mitral valve repair with the Edwards PASCAL System in patients with degenerative mitral regurgitation

Group IV: Abbott Mitraclip System - CLASP IID Active Control 1 Intervention

Transcatheter mitral valve repair with the Abbott Mitraclip System in patients with degenerative mitral regurgitation

Group V: Abbott Mitraclip System - CLASP IIF Active Control 1 Intervention

Transcatheter mitral valve repair with the Abbott Mitraclip System in patients on guideline directed medical therapy with functional mitral 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

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]

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]

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 achieved a high procedural success rate of 96.9% in treating mitral regurgitation under conscious sedation in a study of 211 patients, indicating its efficacy as a treatment option.

The procedure resulted in significant improvements in mitral regurgitation and functional class, with a low mortality rate of 2.8% and a short hospital stay, suggesting it is a safe and efficient alternative to general anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of patients undergoing edge-to-edge mitral valve repair with the Edwards PASCAL transcatheter valve repair system under conscious sedation. Geisler, T., Schreieck, J., Euper, M., et al.[2023]

In a study involving 17 high-risk patients with symptomatic mitral regurgitation, the PASCAL Ace implant system achieved a technical success rate of 100% and a procedural success rate of 94%, indicating its effectiveness in treating this condition.

After one year, 93% of patients had a significant reduction in mitral regurgitation severity (to grade ≤2+), with an 88% survival rate and 94% free from heart failure hospitalization, demonstrating both safety and efficacy of the device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-Year Outcomes of Early, Compassionate Use of the PASCAL Ace Implant System for Transcatheter Mitral Valve Repair. Moonen, A., Chuang, A., Simmons, L., et al.[2023]

The PASCAL system for transcatheter mitral valve repair demonstrated a high technical success rate of 96% in 68 patients, with all patients achieving a reduction in mitral regurgitation (MR) to ≤2+ at discharge.

At 30 days post-procedure, the major adverse event rate was low at 5.9%, and 98% of patients improved to New York Heart Association functional class ≤II, indicating both safety and significant improvement in patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberian experience with PASCAL transcatheter edge-to-edge repair for mitral valve regurgitation. Li, CP., Estévez-Loureiro, R., Freixa, X., et al.[2022]

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 ... The PASCAL Precision transcatheter valve repair system (the PASCAL Precision system) is indicated for the percutaneous reduction of significant, symptomatic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10236790/

One-Year Outcomes of Early, Compassionate Use of the ... The aim of this study is to report 1-year outcomes from the early, compassionate-use observational experience with the novel PASCAL Ace implant system.

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. 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, ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03706833

NCT03706833 | Edwards PASCAL CLASP IID/IIF Pivotal ... To establish the safety and effectiveness of the Edwards PASCAL Transcatheter Valve Repair System in patients with degenerative mitral regurgitation (DMR) ...