TRILUMINATE Pivotal Trial

Study Overview
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Brief Summary
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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).

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

Conditions
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Tricuspid Regurgitation

Intervention / Treatment
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* Device: Tricuspid valve repair


Participation Criteria
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Eligibility Criteria
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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) device. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roll-In<br>TriClip Device treatment for physicians requiring additional training prior to beginning randomized cohort enrollment. | Device: Tricuspid valve repair<br>* Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation<br>|
| Active Comparator: Randomized Cohort<br>TriClip (Device) Group vs. Medical Therapy (Control) Group | Device: Tricuspid valve repair<br>* Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation<br>|
| Experimental: Single Arm<br>Subjects in which it is believed TR is not going to be reduced to moderate or less severity will receive the TriClip device. | Device: Tricuspid valve repair<br>* Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation<br>|
| Experimental: Continued Access Study<br>TriClip Device treatment for eligible patients, while also providing additional experience for operators and supplementary safety and effectiveness data on the device. | Device: Tricuspid valve repair<br>* Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hierarchical composite of number of participants with all-cause mortality or number of participants with tricuspid valve surgery, rate of heart failure hospitalizations, and assessment of quality of life improvement using the KCCQ |  | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TR from severe to moderate or less |  | 30 Days | 
| Freedom from major adverse events (MAE) occurring after procedure attempt |  | 30 Days | 
| Change in Quality of Life as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score | KCCQ score ranges from 0 to 100, with 100 representing the least burden of symptoms | 12 Months | 
| Change in 6 Minute Walk Test (6MWT) |  | 12 Months |