TRILUMINATE Pivotal Trial
- Conditions
- Tricuspid Regurgitation
- Interventions
- Device: TriClipTM Device
- Registration Number
- NCT03904147
- Lead Sponsor
- Abbott Medical Devices
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 572
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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.
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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).
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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.
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New York Heart Association (NYHA) Functional Class II, III or ambulatory class IV
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In the judgment of the TriClip(TM) implanting Investigator, femoral vein access is determined to be feasible and can accommodate a 25 Fr catheter.
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Age ≥18 years at time of consent.
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Subject must provide written informed consent prior to any trial related procedure.
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Systolic pulmonary artery pressure (sPAP) > 70 mmHg or fixed pre-capillary pulmonary hypertension as assessed by right heart catheterization (RHC)
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Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 110 mm Hg
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Any prior tricuspid valve procedure that would interfere with placement of the TriClip(TM) device
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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.
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Pacemaker or ICD leads that would prevent appropriate placement of the TriClip(TM) clip.
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Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg as measured by the ECL
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Left Ventricular Ejection Fraction (LVEF) ≤20%
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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.
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Tricuspid valve anatomy not evaluable by TTE and TEE
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Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated).
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MI or known unstable angina within prior 30 days
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Percutaneous coronary intervention within prior 30 days
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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.
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Cerebrovascular Accident (CVA) within prior 90 days
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Chronic dialysis
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Bleeding disorders or hypercoagulable state
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Active peptic ulcer or active gastrointestinal (GI) bleeding
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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.
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Ongoing infection requiring current antibiotic therapy (if temporary illness, patients may enroll 30 days after discontinuation of antibiotics with no active infection).
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Known allergy or hypersensitivity to device materials
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Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation.
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Life expectancy of less than 12 months
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Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.
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Subject is currently participating in another clinical investigation for valvular heart disease(s).
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomized - Control Group TriClipTM Device Subjects will continue to be managed on medical therapy, per physician discretion Single Arm Group TriClipTM Device Subjects will receive the TriClip device and will continue to be managed on medical therapy, per physician discretion. Continued Access Study (CAS) TriClipTM Device Subjects will undergo TriClip implantation and will continue to be managed on medical therapy, per physician discretion Randomized - Device Group TriClipTM Device Subjects will undergo TriClip implantation and will continue to be managed on medical therapy, per physician discretion
- Primary Outcome Measures
Name Time Method For Randomized Cohort: Hierarchical Composite of All-cause Death or Tricuspid Valve Surgery, Heart Failure Hospitalizations, and KCCQ Improvement 12 Months Analysis of hierarchical composite of all-cause death or tricuspid valve surgery, heart failure hospitalizations, and KCCQ improvement of at least 15 points was performed in ITT population using Finkelstein-Schoenfeld method.
A win ratio was also calculated to descriptively quantify the magnitude of treatment benefits. The win ratio is calculated as the ratio of the number of wins in Device versus Control patients. The primary analysis population consisted of 175 Device patients and 175 Control patients, resulting in 30,625 Device-Control patient pairs (i.e., 175 × 175).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. 12 months This outcome will be assessed as the percentage of subjects meeting the definition of the endpoint.
- Secondary Outcome Measures
Name Time Method For Single-Arm Cohort: The Percentage of Subjects With TR Reduction by at Least 1 Grade at 30-Day Follow-up 30 days For Randomized Cohort: Change in Quality of Life as Assessed by KCCQ Score 12 months minus baseline The mean change in KCCQ score between 12 months and baseline in the Device and Control groups will be compared, while adjusting for the baseline KCCQ score. The primary analysis for this endpoint imputed a KCCQ score of 0 at 12-month visit for all subjects who experienced a heart failure related cardiovascular death or received tricuspid valve surgery prior to completing 12-month follow-up. All KCCQ scores are scaled from 0 (worst) to 100 (best possible status), where the higher score reflects a better health status.
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 30 Days Freedom from major adverse events (MAE) was assessed in the Attempted Procedure population (n=172). MAEs included cardiovascular mortality, new onset renal failure, endocarditis requiring surgery, and non-elective cardiovascular surgery for TriClip device-related AE post-index procedure.
For Randomized Cohort: Tricuspid Regurgitation Reduction to Moderate or Less at 30-Day Visit 30 Days The percentage of subjects with tricuspid regurgitation reduced to moderate or less at 30-day visit in the Device Group will be compared with that in the Control Group. Tricuspid regurgitation severity will be graded on a 5-point scale: trace/mild, moderate, severe (severe 3), massive (severe 4), and torrential (severe 5), which has frequently been used in recent interventional tricuspid studies to categorize tricuspid regurgitation severity. This grading system follows the 2017 ASE guidelines (Zoghbi WA, Adams D, Bonow RO et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2017;30:303-371.), and further stratifies the traditional "severe" category into severe (Severe 3), massive (Severe 4), and torrential (Severe 5).
Recurrent HF Hospitalizations at 24 Months 24 months H0: HR(24M)\>1; H1: HR(24M)≤1
Freedom From All-cause Mortality, Tricuspid Valve Surgery, and Tricuspid Valve Intervention at 24 Months 24 months H0: Survival curves of the two groups through 24 months are the same. H1: Survival curves of the two groups through 24 months are different.
For Randomized Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months 12 Months The primary analysis for this endpoint imputed a 6MWT distance of 0 meters for all subjects who experienced a heart failure related cardiovascular death or received tricuspid valve surgery prior to completing 12-month follow-up. Subjects who were unable to exercise due to cardiac reasons were also assigned a 6MWT distance of 0 meters at 12-month follow-up. Other subjects with missing 6MWT distance at either baseline or 12-month follow-up were excluded from the analysis.
For Single-Arm Cohort: Rate of Freedom From MAE Through 30 Days 30 days Freedom from MAE occurring after procedure attempt (femoral vein puncture) at 30 days. Components of MAE consist of Cardiovascular Mortality, New Onset Renal Failure, Endocarditis Requiring Surgery, and Non-Elective Cardiovascular Surgery for TriClip device-related AE post-index procedure.
For Single-Arm Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months 12 months This analysis imputed a 6MWT distance of 0 meters for all subjects who were unable to exercise due to cardiac reasons. However, there were no subjects unable to exercise due to cardiac reasons and therefore no imputation was performed. Subjects with missing 6MWT distance at either baseline or 12-month follow-up were excluded from the analysis.
Trial Locations
- Locations (76)
Delray Medical Center
🇺🇸Delray Beach, Florida, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Scripps Green Hospital
🇺🇸La Jolla, California, United States
Tucson Medical Center
🇺🇸Tucson, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
El Camino Hospital
🇺🇸Mountain View, California, United States
Providence Medical Foundation (St. Joseph Hospital)
🇺🇸Orange, California, United States
JFK Medical Center
🇺🇸Atlantis, Florida, United States
Morton Plant Valve Clinic
🇺🇸Clearwater, Florida, United States
Manatee Memorial Hospital
🇺🇸Bradenton, Florida, United States
Tallahassee Research Institute
🇺🇸Tallahassee, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
Palm Beach Garden Medical Center
🇺🇸Palm Beach Gardens, Florida, United States
Piedmont Heart Institute
🇺🇸Atlanta, Georgia, United States
St. Vincent Hospital
🇺🇸Indianapolis, Indiana, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Northshore University HealthSystem
🇺🇸Evanston, Illinois, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Cardiovascular Institute of the South
🇺🇸Houma, Louisiana, United States
MedStar Health Research Institute
🇺🇸Hyattsville, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Buffalo General Hospital
🇺🇸Buffalo, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
New York-Presbyterian/Columbia University Medical Center
🇺🇸New York, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor Scott and White Heart and Vascular Hospital
🇺🇸Dallas, Texas, United States
Methodist Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Sentara Norfolk General Hospital
🇺🇸Norfolk, Virginia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Science Centre
🇨🇦Toronto, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Institut de Cardiologie de Montreal (Montreal Heart Inst.)
🇨🇦Montréal, Quebec, Canada
München Grosshadern
🇩🇪München, Bavaria, Germany
Universitätsklinikum Bonn AdöR
🇩🇪Bonn, North Rhine-Westphalia, Germany
Herzzentrum Leipzig GmbH
🇩🇪Leipzig, Saxony, Germany
Hospital Clinic I Provincial de Barcelona
🇪🇸Barcelona, Catalonia, Spain
Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Cardiovascular Research Institute of Kansas
🇺🇸Wichita, Kansas, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
The Royal Victoria
🇨🇦Montréal, Quebec, Canada
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Scottsdale Healthcare Shea
🇺🇸Scottsdale, Arizona, United States
UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Rhineland-Palatinate, Germany
California Pacific Medical Center
🇺🇸San Francisco, California, United States
St. Thomas Hospital
🇺🇸Nashville, Tennessee, United States
Centennial Heart Cardiovascular Consultants
🇺🇸Nashville, Tennessee, United States
Ospedale San Raffaele - Cardiac
🇮🇹Milano, Lombard, Italy
Hamilton Health Science Centre
🇨🇦Hamilton, Ontario, Canada
University Hospital - University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
St. Joseph's Hospital & Medical Center
🇺🇸Phoenix, Arizona, United States
Arizona Cardiovascular Research Center
🇺🇸Phoenix, Arizona, United States
Phoenix Cardiovascular Research Group
🇺🇸Phoenix, Arizona, United States
Providence Heart and Vascular Institute
🇺🇸Portland, Oregon, United States
Aurora Medical Group
🇺🇸Milwaukee, Wisconsin, United States
Los Robles Regional Medical Center
🇺🇸Thousand Oaks, California, United States
Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Novant Health Heart and Vascular Research Institute
🇺🇸Charlotte, North Carolina, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio Health Research Institute
🇺🇸Columbus, Ohio, United States
Sutter Medical Center, Sacramento
🇺🇸Sacramento, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Yale New Haven
🇺🇸New Haven, Connecticut, United States
University of California - Davis Medical Center
🇺🇸Sacramento, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Austin Heart
🇺🇸Austin, Texas, United States
Montefiore Medical Center - Moses Division
🇺🇸Bronx, New York, United States