Clinical trial NCT04097145: Edwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial
Official title: A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Tricuspid Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System and Optimal Medical Therapy (OMT) Compared to OMT Alone in Patients With Tricuspid Regurgitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tricuspid Regurgitation
Tricuspid Valve Insufficiency
Tricuspid Valve Disease
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2019-09-20
Enrollment: 870
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 Repair System in patients with symptomatic severe tricuspid regurgitation who have been determined to be at an intermediate or greater estimated risk of mortality with tricuspid valve surgery by the cardiac surgeon with concurrence by the local Heart Team

Detailed description: A Prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter tricuspid valve repair with the Edwards PASCAL Transcatheter Valve Repair System and optimal medical therapy (OMT) compared to OMT alone in patients with tricuspid regurgitation. Patients will be seen for follow-up visits at discharge, 30 days, 3 months, 6 months, and annually through 5 years.

Eligibility criteria: Inclusion Criteria:

* Eighteen (18) years of age or older
* Despite medical therapy, per the local Heart Team, patient has signs of TR, symptoms from TR, or prior heart failure hospitalization from TR.
* Severe or greater tricuspid regurgitation
* New York Heart Association (NYHA) Class II-IVa or heart failure hospitalization in the prior 12 months
* Patient is at an intermediate or greater estimated risk of mortality with tricuspid valve surgery as determined by the cardiac surgeon with concurrence by the local Heart Team
* Patient is able and willing to give informed consent, follow protocol procedures, and comply with follow-up visit requirements

Exclusion Criteria:

* Tricuspid valve anatomy not evaluable by TTE or TEE
* Tricuspid valve anatomy precludes proper device deployment and function
* Patient with refractory heart failure requiring, advanced intervention (i.e. patient has or will need left ventricular assist device, or transplantation) (ACC/AHA Stage D heart failure)
* Presence of trans-tricuspid pacemaker or defibrillator leads which meet one of the following:

  1. Would prevent proper TR reduction due to interaction of the lead with the leaflets
  2. Were implanted in the RV within the last 90 days prior to the point of enrollment
* Primary non-degenerative tricuspid disease
* Previous tricuspid valve repair or replacement that would interfere with placement of PASCAL
* Clinically significant, untreated coronary artery disease requiring revascularization, unstable angina, evidence of acute coronary syndrome, recent myocardial infarction
* Significant intra-cardiac mass, thrombus, or vegetation per echo core lab assessment
* Deep vein thrombosis (DVT) or pulmonary embolism (PE) in the last 90 days
* Recent Stroke
* Active gastrointestinal (GI) bleeding
* Presence of infiltrative cardiomyopathy or valvulopathy (including carcinoid, amyloidosis, sarcoidosis, hemochromatosis) or significant congenital heart disease, including but not limited to atrial septal defect, RV dysplasia, and arrhythmogenic RV
* Need for emergent or urgent surgery for any reason, any planned cardiac surgery within the next 12 months (365 days), or any planned percutaneous cardiac procedure within the next 90 days
* Any of the following cardiovascular procedures:

  1. Percutaneous coronary, intracardiac, or endovascular intervention within the last 30 days prior to the point of enrollment
  2. Carotid surgery within 30 days prior to the point of enrollment
  3. Direct current cardioversion within the last 30 days prior to the point of enrollment
  4. Leadless RV pacemaker implant within the last 30 days prior to the point of enrollment
  5. Cardiac surgery within 90 days prior to the point of enrollment
* Severe aortic, mitral and/or pulmonic valve stenosis and/or regurgitation
* Known history of untreated severe symptomatic carotid stenosis or asymptomatic carotid stenosis
* Active endocarditis within the last 90 days or infection requiring antibiotic therapy within the last 14 days
* Patient is oxygen-dependent or requires continuous home oxygen
* Pregnant, breastfeeding, or planning pregnancy within the next 12 months (365 days)
* 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
* Patient has other medical, social, or psychological conditions that preclude appropriate consent and follow-up, or the patient is under guardianship
* Any patient considered to be vulnerable

Primary outcomes:
measure: Composite endpoint including all-cause mortality, RVAD implantation or heart transplant, tricuspid valve intervention, heart failure hospitalizations, and Quality of Life improvement (measured by KCCQ score)
timeFrame: 12 months
Secondary outcomes:
measure: 1 Grade Reduction in TR Severity
timeFrame: 6, 12 months
measure: Quality of Life (QOL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: 3, 6, and 12 months
measure: All Cause Mortality
timeFrame: 12 months, 24 months
measure: Death and Heart Failure Hospitalizations
timeFrame: 12 months
measure: All-cause Hospitalization
timeFrame: 12 months
measure: Right ventricular end-diastolic diameter (RVEDD mid)
timeFrame: 12 months
measure: Major Adverse Events (MAEs)
timeFrame: 30 days
measure: Reduction in TR grade
timeFrame: Intraprocedural post-implantation
measure: All-Cause Mortality
timeFrame: 12 months, annually through 5 years
measure: Heart failure hospitalizations
timeFrame: 12 months, annually through 5 years
measure: Non-elective tricuspid valve re-intervenitions (percutaneous or surgical)
timeFrame: 12 months, annually through 5 years
measure: Durable RVAD implantation or heart transplant
timeFrame: 12 months, annually through 5 years
measure: Need for paracentesis
timeFrame: 12 months, annually through 5 years
measure: All cause mortality or the first heart failure hospitalization for patients with massive or torrential TR at baseline
timeFrame: 12, 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center Healthcare
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: La Jolla
country: United States
facility: SCPMG - Kaiser San Diego
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
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: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Gainesville
country: United States
facility: The Cardiac and Vascular Institute Research Foundation
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Naples
country: United States
facility: NCH Healthcare System
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown / Emory University - St. Joseph's Hospital
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Healthcare, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Heart Center Cardiovascular Research Institute
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
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: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak
state: Michigan
city: Saginaw
country: United States
facility: St. Mary's of Ascension Research
state: Michigan
city: Maplewood
country: United States
facility: Fairview Health Services
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Missoula
country: United States
facility: Providence St. Patrick Hospital
state: Montana
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Health Systems
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center / Arts Pavilion / Hutchinson Metro Center Clinic / Weiler Hospital / Moses Hospital
state: New York
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center/NYPH
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital, Northwell Health /Northshore University Hospital Manhasset
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: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center Fargo
state: North Dakota
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth-Bethesda North Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Research Group
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute at Hillcrest Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Presbyterian Medical Center / Hospital of the University of Pennsylvania
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health Cardiovascular Institute/UPMC Pinnacle
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Heart Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: HCA Houston Healthcare Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: UTHealth/Memorial Hermann Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White - The Heart Hospital - Plano
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Saint George
country: United States
facility: St. George Regional Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Roanoke
country: United States
facility: Carilion Medical Center
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Services
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Québec City
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
state: Quebec
Study officials:
affiliation: Columbia University
name: Martin B. Leon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Scott and White Health
name: Michael J. Mack, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Charles Davidson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Health San Antonio
name: Allen Anderson, MD
role: STUDY_CHAIR
affiliation: University of Michigan
name: Gorav Ailawadi, MD
role: STUDY_CHAIR
References: