Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial

Conditions

Degenerative Mitral Valve Disease, Functional Mitral Regurgitation, Mitral Insufficiency, Mitral Regurgitation

Brief summary

To establish the safety and effectiveness of the Edwards PASCAL Transcatheter Valve Repair System in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT)

Detailed description

A prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter mitral valve repair with the Edwards PASCAL Transcatheter Valve Repair System compared to Abbott MitraClip in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT) Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 5 years.

Al-Abcha A, Lim DS, Hausleiter J, Smith RL, Zahr F, Chadderdon S, Makkar R, Makar MM, von Bardeleben RS, Ruf TF, Gößler T, Kipperman RM, Rassi AN, Ku IA, Nabauer M, Szerlip M, Wang Z, Goldman S, Hawthorne KM, Koulogiannis K, Marcoff L, Gillam LD, Guerrero ME, CLASP IID Pivotal Trial Investigators.

2025-11-011 citations

10.1016/j.jcin.2025.08.039

CLASP IID Trial and Registry: 2-Year Outcomes of Transcatheter Repair for Degenerative Mitral Regurgitation.

Makkar R, Zahr F, Chakravarty T, Chadderdon S, Makar M, Ruf TF, Kipperman RM, Rassi AN, Hausleiter J, Smith RL, Szerlip M, Goldman S, Lim DS, Inglessis-Azuaje I, Yadav P, Lurz P, Kister T, Davidson CJ, Mumtaz M, Gada H, Kar S, Kodali SK, Laham R, Hiesinger W, Fam NP, Keßler M, O'Neill WW, Whisenant B, Kliger C, Rudolph V, Hermiller J, Dhoble A, Smalling R, Latib A, Lazkani M, Choo J, Garcia S, Rodés-Cabau J, Schofer N, Baldus S, Kapadia S, Koulogiannis K, Marcoff L, Gillam LD, von Bardeleben RS, CLASP IID Trial and Registry Investigators.

2025-10-01

10.1016/j.jcin.2025.07.014

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

Marcoff L, Koulogiannis K, Aldaia L, Mediratta A, Chadderdon SM, Makar MM, Ruf TF, Gößler T, Zaroff JG, Leung GK, Ku IA, Nabauer M, Grayburn PA, Wang Z, Hawthorne KM, Fowler DE, Dal-Bianco JP, Vannan MA, Bevilacqua C, Meineri M, Ender J, Forner AF, Puthumana JJ, Mansoor AH, Lloyd DJ, Voskanian SJ, Ghobrial A, Hahn RT, Mahmood F, Haeffele C, Ong G, Schneider LM, Wang DD, Sekaran NK, Koss E, Mehla P, Harb S, Miyasaka R, Ivannikova M, Stewart-Dehner T, Mitchel L, Raissi SR, Kalbacher D, Biswas S, Ho EC, Goldberg Y, Smith RL, Hausleiter J, Lim DS, Gillam LD, CLASP IID Pivotal Trial Investigators.

2023-12-134 citations

10.1016/j.jcmg.2023.09.015

Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation.

Hausleiter J, Lim DS, Gillam LD, Zahr F, Chadderdon S, Rassi AN, Makkar R, Goldman S, Rudolph V, Hermiller J, Kipperman RM, Dhoble A, Smalling R, Latib A, Kodali SK, Lazkani M, Choo J, Lurz P, O'Neill WW, Laham R, Rodés-Cabau J, Kar S, Schofer N, Whisenant B, Inglessis-Azuaje I, Baldus S, Kapadia S, Koulogiannis K, Marcoff L, Smith RL, PASCAL IID Registry Investigators.

2023-02-0144 citations

10.1016/j.jacc.2022.11.034

Randomized Comparison of Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

Lim DS, Smith RL, Gillam LD, Zahr F, Chadderdon S, Makkar R, von Bardeleben RS, Kipperman RM, Rassi AN, Szerlip M, Goldman S, Inglessis-Azuaje I, Yadav P, Lurz P, Davidson CJ, Mumtaz M, Gada H, Kar S, Kodali SK, Laham R, Hiesinger W, Fam NP, Keßler M, O'Neill WW, Whisenant B, Kliger C, Kapadia S, Rudolph V, Choo J, Hermiller J, Morse MA, Schofer N, Gafoor S, Latib A, Koulogiannis K, Marcoff L, Hausleiter J, CLASP IID Pivotal Trial Investigators.

2022-09-17100 citations

10.1016/j.jcin.2022.09.005

Interventions

DEVICEEdwards PASCAL System

Transcatheter mitral valve repair with the Edwards PASCAL System

DEVICEAbbott Mitraclip System

Transcatheter mitral valve repair with the Abbott Mitraclip System

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Eighteen (18) years of age or older * Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow-up visit requirements. * Patient is determined to be at prohibitive risk for mitral valve surgery by the heart team (CLASP IID cohort only). * Patient is on stable heart failure medications/Guideline Directed Medical Therapy (CLASP IIF cohort only) * Patient is determined to be a candidate for transcatheter mitral valve repair by the heart team for both PASCAL and MitraClip * Mitral regurgitation (3+ to 4+) by echo * Suitable valve and regurgitant jet morphology * Elevated corrected BNP \> 400 pg/ml or corrected NT-pro BNP of \> 900 pg/ml or heart failure hospitalization within the past 12 months (CLASP IIF cohort only) * LVEF ≥ 20% (and ≤ 50%; CLASP IIF cohort only)

Exclusion criteria

* Patient in whom a TEE is contraindicated or screening TEE is unsuccessful * Mitral valve anatomy which may preclude proper PASCAL or MitraClip access, use and/or deployment or sufficient reduction in mitral regurgitation * Patient with refractory heart failure requiring advanced intervention (i.e. left ventricular assist device, Status ≤5 heart transplantation) (ACC/AHA Stage D heart failure) * Clinically significant, untreated coronary artery disease * Recent stroke * Other severe valve disorders requiring intervention * Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months * Any prior mitral valve surgery or transcatheter mitral valve procedure (excluding chordal replacement or surgical annuloplasty repair) * Severe tricuspid regurgitation or tricuspid valve disease requiring surgery * Active rheumatic heart disease or rheumatic etiology for MR * Severe aortic stenosis or regurgitation * Known history of untreated, severe carotid stenosis * Recent deep vein thrombosis (DVT) or pulmonary embolism (PE) * Severe COPD * Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to intervention and be adherent to an accepted method of contraception * 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 * Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients under guardianship

Design outcomes

Primary

Measure	Time frame
PASCAL is not inferior to MitraClip with respect to the proportion of patients with major adverse events (MAE). The primary safety endpoint is a composite of Major Adverse Events (MAEs).	30 days.
PASCAL is not inferior to Mitraclip with respect to the proportion of patients with MR severity reduction as measured by echocardiography using a scale of 0-4+ for the CLASP IID Cohort.	6 months
PASCAL is not inferior to Mitraclip with respect to the time to first heart failure hospitalization or death for the CLASP IIF Cohort only.	From date of randomization until date of first heart failure hospitalization or death, through 5 year follow-up

Secondary

Measure	Time frame	Description
Rates of various adverse events	6 months; 12 months	Rates of various adverse events at 6 and 12 months
Functional Improvement (increase in 6 minute walk test in meters)	30 days , 6 months, 1 year	Increase in 6 minute walk test in meters
Functional improvement (quality of life) as assessed using the Kansas City Cardiomyopathy Questionnaire through 2 years	30 days , 6 months, 1 year, 2 year	Number of points of improvement on a scale of 0-100 in Kansas City Cardiomyopathy Questionnaire, with higher scores associated with higher Quality of Life
Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (SF-36) questionnaire through 2 years	30 days, 6 months, 1 year, 2 year	Number of points of improvement on a scale of 0-100 in Short Form Health Survey (SF-36) questionnaire, with higher totals associated with higher Quality of Life
Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (EQ-5D-5L) questionnaire through	30 days, 6 months, 1 year, 2 year	Number of points of improvement on a scale of 1-100 in Short Form Health Survey (EQ-5D-5L) questionnaire, with higher totals associated with higher Quality of Life

Countries

Canada, Germany, Switzerland, United States

Contacts

PRINCIPAL_INVESTIGATORScott Lim, MD

University of Virginia

PRINCIPAL_INVESTIGATORRobert Smith, MD

The Heart Hospital Baylor Plano

PRINCIPAL_INVESTIGATORLinda Gillam, MD

Morristown Medical Center

PRINCIPAL_INVESTIGATORVinod Thourani, MD

Piedmont Healthcare

PRINCIPAL_INVESTIGATORPaul Grayburn, MD

The Heart Hospital Baylor Plano

PRINCIPAL_INVESTIGATORBrian K Whisenant, MD

Intermountain Health Care, Inc.

PRINCIPAL_INVESTIGATORJörg Hausleiter, MD

LMU München, Campus Gorsshadern

PRINCIPAL_INVESTIGATORRalph Stephan von Bardeleben, MD

/ Universitätsmedizin Mainz- Zentrum für Kardiologie

Outcome results

None listed