Clinical trial NCT03706833: Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial
Official title: Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial (CLASP IID/IIF): 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 Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Degenerative Mitral Valve Disease
Mitral Regurgitation
Mitral Insufficiency
Functional Mitral Regurgitation
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2018-10-16
Enrollment: 1247
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: 30 days.
measure: 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.
timeFrame: 6 months
measure: PASCAL is not inferior to Mitraclip with respect to the time to first heart failure hospitalization or death for the CLASP IIF Cohort only.
timeFrame: From date of randomization until date of first heart failure hospitalization or death, through 5 year follow-up
Secondary outcomes:
measure: Rates of various adverse events
timeFrame: 6 months; 12 months
measure: Functional Improvement (increase in 6 minute walk test in meters)
timeFrame: 30 days , 6 months, 1 year
measure: Functional improvement (quality of life) as assessed using the Kansas City Cardiomyopathy Questionnaire through 2 years
timeFrame: 30 days , 6 months, 1 year, 2 year
measure: 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
timeFrame: 30 days, 6 months, 1 year, 2 year
measure: Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (EQ-5D-5L) questionnaire through
timeFrame: 30 days, 6 months, 1 year, 2 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Abrazo Arizona Heart Hospital
state: Arizona
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: Tucson
country: United States
facility: TMC Healthcare
state: Arizona
city: La Jolla
country: United States
facility: Scripps Memorial Hospital La Jolla
state: California
city: Los Angeles
country: United States
facility: PIH Health Good Samaritan Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Orange
country: United States
facility: UC Irvine
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center-Sacramento
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Sutter Bay Area
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital and Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: The Cardiac and Vascular Institute Research Foundation
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai
state: Florida
city: Naples
country: United States
facility: NCH Healthcare System Naples
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital and Emory University Hospital Midtown
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Advocate Health & Hospitals Corp/Edward Heart Hospital
state: Illinois
city: Carmel
country: United States
facility: St. Vincent Heart Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Woman's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Maplewood
country: United States
facility: Fairview Health Services
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular Center
state: Minnesota
city: Kansas City
country: United States
facility: St.Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University/Barnes Jewish Hospital
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers-RWJMS
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital and North Shore University
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Charlotte
country: United States
facility: Atrium Health/Sanger Heart & Vascular Institute
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Health Baptist Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania/Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health Cardiovascular Institute/ UPMC Pinnacle Harrisburg
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: York
country: United States
facility: WellSpan York Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: Baptist Memorial Hospital Memphis
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Heart at Saint Thomas West
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas
state: Texas
city: Houston
country: United States
facility: HCA Houston Healthcare Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Chippenham Johnston & Willis Medical Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Vancouver
country: Canada
facility: St. Pauls Hospital
state: British Columbia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Québec
country: Canada
facility: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) ULaval
city: Bad Oeynhausen
country: Germany
facility: Klinik für Allgemeine und Interventionelle Kardiologie/Angiologie, Herz- und Diabeteszentrum NRW, Universitätsklinik der Ruhr-Universität Bochum
city: Cologne
country: Germany
facility: Herzzentrum Universitätsklinikum Koln
city: Dresden
country: Germany
facility: Herrzentrum Dresden GmbH Universitätklinik an der Technischen Universität Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR) Klinik für Kardiologie und Angiologie am Westdeutschen Herz- und Gefäßzentrum
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen Medizinische Klinik I, Innere Medizin/ Kardiologie
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg GmbH (UHZ) Klinik und Poliklinik für Allgemeneine und Interventionelle Kardiologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg Klinik für Kardiologie, Angiologie, Pneumologie
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig Universitätsklinik für Kardiologie
city: Mainz
country: Germany
facility: Zentrum für Kardiologie - Kardiologie I Universitätsmedizin der Johannes Gutenberg Universität Mainz
city: München
country: Germany
facility: Medizinische Klinik I LMU München Campus Grosshadern
city: Siegburg
country: Germany
facility: Helios Klinikum Siegburg
city: Ulm
country: Germany
facility: ULM University Zentrum für Innere Medizin Klinik für Innere Medizin II
city: Bern
country: Switzerland
facility: University Hospital Bern
Study officials:
affiliation: University of Virginia
name: Scott Lim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Heart Hospital Baylor Plano
name: Robert Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Morristown Medical Center
name: Linda Gillam, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Healthcare
name: Vinod Thourani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Heart Hospital Baylor Plano
name: Paul Grayburn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Intermountain Medical Center
name: Brian K Whisenant, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU München, Campus Gorsshadern
name: Jörg Hausleiter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: / Universitätsmedizin Mainz- Zentrum für Kardiologie
name: Ralph Stephan von Bardeleben, MD
role: PRINCIPAL_INVESTIGATOR
References: