Clinical trial NCT03904147: TRILUMINATE Pivotal Trial
Official title: Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tricuspid Regurgitation
Keywords: ABT-CIP-10249
Tricuspid
Cardiovascular
Pivotal
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2019-04-05
Enrollment: 572
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: The primary objective of this trial is to demonstrate the safety and effectiveness of the TriClip device in improving clinical outcomes in symptomatic patients with severe tricuspid regurgitation (TR), who are at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery. This randomized controlled trial will compare the investigational device (TriClip device) to Control (Medical Therapy).


Eligibility criteria: Inclusion Criteria:

* In the judgment of the site local heart team, subject has been adequately treated per applicable standards (including medical management) and stable for at least 30 days as follows:

  * Optimized medical therapy for treatment of TR (e.g. diuretics).
  * Medical and/or device therapy, for mitral regurgitation, atrial fibrillation, coronary artery disease and heart failure.
  * The Eligibility Committee will confirm that the subject has been adequately treated medically.
* Subject is symptomatic with Severe TR despite being optimally treated as described above. TR severity is determined by the assessment of a qualifying TTE and confirmed by the ECL. The ECL will also request a TEE to confirm TR etiology. Note: If any cardiac procedure(s) occur after eligibility was determined, TR severity will need to be re-assessed 30 days after the cardiac procedure(s).
* The cardiac surgeon of the site local heart team concur that the patient is at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery.
* New York Heart Association (NYHA) Functional Class II, III or ambulatory class IV
* In the judgment of the TriClip(TM) implanting Investigator, femoral vein access is determined to be feasible and can accommodate a 25 Fr catheter.
* Age ≥18 years at time of consent.
* Subject must provide written informed consent prior to any trial related procedure.

Exclusion Criteria:

* Systolic pulmonary artery pressure (sPAP) \> 70 mmHg or fixed pre-capillary pulmonary hypertension as assessed by right heart catheterization (RHC)
* Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 110 mm Hg
* Any prior tricuspid valve procedure that would interfere with placement of the TriClip(TM) device
* Indication for left-sided (e.g. severe aortic stenosis, severe mitral regurgitation) or pulmonary valve correction prior 60 days. Note: Patients with concomitant Mitral and tricuspid valve disease will have the option of getting their MR treated, and wait 60 days prior to being reassessed for the trial.
* Pacemaker or ICD leads that would prevent appropriate placement of the TriClip(TM) clip.
* Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg as measured by the ECL
* Left Ventricular Ejection Fraction (LVEF) ≤20%
* Tricuspid valve leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in TR. This may include:

  * Evidence of calcification in the grasping area
  * Presence of a severe coaptation defect (\> 2cm) of the tricuspid leaflets
  * Severe leaflet defect(s) preventing proper device placement
  * Ebstein Anomaly - Identified by having a normal annulus position while the valve leaflets are attached to the walls and septum of the right ventricle.
* Tricuspid valve anatomy not evaluable by TTE and TEE
* Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated).
* MI or known unstable angina within prior 30 days
* Percutaneous coronary intervention within prior 30 days
* Hemodynamic instability defined as systolic pressure \< 90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or intra-aortic balloon pump or other hemodynamic support device.
* Cerebrovascular Accident (CVA) within prior 90 days
* Chronic dialysis
* Bleeding disorders or hypercoagulable state
* Active peptic ulcer or active gastrointestinal (GI) bleeding
* Contraindication, allergy or hypersensitivity to dual antiplatelet and anticoagulant therapy.

  * Note: Contraindication to either antiplatelet or anticoagulant therapy (individually not both therapies) is not an exclusion criterion.
* Ongoing infection requiring current antibiotic therapy (if temporary illness, patients may enroll 30 days after discontinuation of antibiotics with no active infection).
* Known allergy or hypersensitivity to device materials
* Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation.
* Life expectancy of less than 12 months
* Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.
* Subject is currently participating in another clinical investigation for valvular heart disease(s).
* Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation follow-up period. Female subjects of child-bearing potential are required to have a negative pregnancy test done within 7 days of the baseline visit per site standard test. Female patients of childbearing potential should be instructed to use safe contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release.) It is accepted, in certain cases, to include subjects having a sterilized regular partner or subjects using a double barrier contraceptive method.
* Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.

Primary outcomes:
measure: For Randomized Cohort: Hierarchical Composite of All-cause Death or Tricuspid Valve Surgery, Heart Failure Hospitalizations, and KCCQ Improvement
timeFrame: 12 Months
measure: For Single-Arm Cohort: Rate of Survival Through 12 Months With a Quality of Life Improvement (Assessed Using KCCQ Overall Score) of at Least 10 Points Compared to Baseline.
timeFrame: 12 months
Secondary outcomes:
measure: For Randomized Cohort - Device Group Only: Rate of Kaplan-Meier Estimate (SE) of Freedom From Major Adverse Events (MAE) Occurring Within 30 Days Post-procedure
timeFrame: 30 Days
measure: For Randomized Cohort: Change in Quality of Life as Assessed by KCCQ Score
timeFrame: 12 months minus baseline
measure: For Randomized Cohort: Tricuspid Regurgitation Reduction to Moderate or Less at 30-Day Visit
timeFrame: 30 Days
measure: For Randomized Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months
timeFrame: 12 Months
measure: For Single-Arm Cohort: The Percentage of Subjects With TR Reduction by at Least 1 Grade at 30-Day Follow-up
timeFrame: 30 days
measure: For Single-Arm Cohort: Rate of Freedom From MAE Through 30 Days
timeFrame: 30 days
measure: For Single-Arm Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months
timeFrame: 12 months
measure: Recurrent HF Hospitalizations at 24 Months
timeFrame: 24 months
measure: Freedom From All-cause Mortality, Tricuspid Valve Surgery, and Tricuspid Valve Intervention at 24 Months
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Hospital - University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Shea
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Orange
country: United States
facility: Providence Medical Foundation (St. Joseph Hospital)
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center, Sacramento
state: California
city: Sacramento
country: United States
facility: University of California - Davis Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Regional Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven
state: Connecticut
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Bradenton
country: United States
facility: Manatee Memorial Hospital
state: Florida
city: Clearwater
country: United States
facility: Morton Plant Valve Clinic
state: Florida
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Palm Beach Gardens
country: United States
facility: Palm Beach Garden Medical Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Northshore University HealthSystem
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Boston
country: United States
facility: Brigham and Women'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: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Division
state: New York
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian/Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular Research Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Portland
country: United States
facility: Providence Heart and Vascular Institute
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Centennial Heart Cardiovascular Consultants
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Hospital
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital of San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora Medical Group
state: Wisconsin
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montreal (Montreal Heart Inst.)
state: Quebec
city: Montréal
country: Canada
facility: The Royal Victoria
state: Quebec
city: München
country: Germany
facility: München Grosshadern
state: Bavaria
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AdöR
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz
state: Rhineland-Palatinate
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
state: Saxony
city: Milano
country: Italy
facility: Ospedale San Raffaele - Cardiac
state: Lombard
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
state: Catalonia
Study officials:
affiliation: Abbott Structural Heart
name: Meghan Griffin, PhD
role: STUDY_DIRECTOR
affiliation: Icahn School of Medicine at Mount Sinai
name: David Adams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allina Health System
name: Paul Sorajja, MD
role: PRINCIPAL_INVESTIGATOR
References: