TRILUMINATE Pivotal Trial

Tricuspid Regurgitation Clinical Trial

Official title:

Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03904147
• Other study ID #: ABT-CIP-10249
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 21, 2019
• Est. completion date: April 2029

Study information

• Verified date: April 2024
• Source: Abbott Medical Devices
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 572
• Est. completion date: April 2029
• Est. primary completion date: November 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Tricuspid Regurgitation
• Tricuspid Valve Insufficiency

Intervention

Device:
• TriClipTM Device
Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation

Locations

Country	Name	City	State
Canada	Hamilton Health Science Centre	Hamilton	Ontario
Canada	Institut de Cardiologie de Montreal (Montreal Heart Inst.)	Montréal	Quebec
Canada	The Royal Victoria	Montréal	Quebec
Canada	Ottawa Heart Institute	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Germany	Universitätsklinikum Bonn AdöR	Bonn	North Rhine-Westphalia
Germany	Herzzentrum Leipzig GmbH	Leipzig	Saxony
Germany	UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz	Mainz	Rhineland-Palatinate
Germany	München Grosshadern	München	Bavaria
Italy	Ospedale San Raffaele - Cardiac	Milano	Lombard
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona	Catalonia
United States	Albany Medical Center	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	JFK Medical Center	Atlantis	Florida
United States	University of Colorado Hospital	Aurora	Colorado
United States	Austin Heart	Austin	Texas
United States	University Hospital - University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Manatee Memorial Hospital	Bradenton	Florida
United States	Montefiore Medical Center - Moses Division	Bronx	New York
United States	Buffalo General Hospital	Buffalo	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Novant Health Heart and Vascular Research Institute	Charlotte	North Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	Morton Plant Valve Clinic	Clearwater	Florida
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio Health Research Institute	Columbus	Ohio
United States	Baylor Scott and White Heart and Vascular Hospital	Dallas	Texas
United States	Delray Medical Center	Delray Beach	Florida
United States	Northshore University HealthSystem	Evanston	Illinois
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Cardiovascular Institute of the South	Houma	Louisiana
United States	The Methodist Hospital	Houston	Texas
United States	MedStar Health Research Institute	Hyattsville	Maryland
United States	St. Vincent Hospital	Indianapolis	Indiana
United States	Kansas University Medical Center	Kansas City	Kansas
United States	Scripps Green Hospital	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Baptist Hospital of Miami	Miami	Florida
United States	Aurora Medical Group	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	El Camino Hospital	Mountain View	California
United States	Intermountain Medical Center	Murray	Utah
United States	Centennial Heart Cardiovascular Consultants	Nashville	Tennessee
United States	St. Thomas Hospital	Nashville	Tennessee
United States	Yale New Haven	New Haven	Connecticut
United States	Mount Sinai Hospital	New York	New York
United States	New York-Presbyterian/Columbia University Medical Center	New York	New York
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Providence Medical Foundation (St. Joseph Hospital)	Orange	California
United States	Palm Beach Garden Medical Center	Palm Beach Gardens	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Cardiovascular Research Center	Phoenix	Arizona
United States	Phoenix Cardiovascular Research Group	Phoenix	Arizona
United States	St. Joseph's Hospital & Medical Center	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence Heart and Vascular Institute	Portland	Oregon
United States	Sutter Medical Center, Sacramento	Sacramento	California
United States	University of California - Davis Medical Center	Sacramento	California
United States	Methodist Hospital of San Antonio	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	Scottsdale Healthcare Shea	Scottsdale	Arizona
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Tallahassee Research Institute	Tallahassee	Florida
United States	Los Robles Regional Medical Center	Thousand Oaks	California
United States	Tucson Medical Center	Tucson	Arizona
United States	Cardiovascular Research Institute of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Abbott Medical Devices

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For Randomized Cohort: Hierarchical Composite of All-cause Death or Tricuspid Valve Surgery, Heart Failure Hospitalizations, and KCCQ Improvement	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).	12 Months
Primary	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.	This outcome will be assessed as the percentage of subjects meeting the definition of the endpoint.	12 months
Secondary	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	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.	30 Days
Secondary	For Randomized Cohort: Change in Quality of Life as Assessed by KCCQ Score	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.	12 months minus baseline
Secondary	For Randomized Cohort: Tricuspid Regurgitation Reduction to Moderate or Less at 30-Day Visit	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).	30 Days
Secondary	For Randomized Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 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.	12 Months
Secondary	For Single-Arm Cohort: The Percentage of Subjects With TR Reduction by at Least 1 Grade at 30-Day Follow-up		30 days
Secondary	For Single-Arm Cohort: Rate of Freedom From MAE Through 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.	30 days
Secondary	For Single-Arm Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 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.	12 months
Secondary	Recurrent HF Hospitalizations at 24 Months	H0: HR(24M)>1; H1: HR(24M)=1	24 months
Secondary	Freedom From All-cause Mortality, Tricuspid Valve Surgery, and Tricuspid Valve Intervention at 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.	24 months