Innoventric Trillium™ Stent Graft First-in-Human (FIH) Study

Study Overview
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Brief Summary
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A prospective, single-arm, multi-center first-in-human (FIH) study to evaluate the safety and performance of the Innoventric Trillium™ Stent Graft System. Twenty (20) patients in 8 investigational sites will be enrolled. All enrolled study patients will be assessed at baseline, during the procedure, at discharge, after 1 month, 3 months, 6 months, 1 year, 1.5 years, 2 years, and 3 years following the index procedure.

Official Title
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Prospective, Single Arm, Multi-center, First-in-human (FIH) Study to Assess the Safety and Performance of the Innoventric Trillium™ Stent Graft for the Treatment of Severe Tricuspid Regurgitation (TR)

Conditions
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Tricuspid Regurgitation

Intervention / Treatment
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* Device: Trillium™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled patients must meet ALL the following criteria: Age >40 (no upper limit) Patient has clinically significant TR graded as severe based on the presence of systolic hepatic vein flow reversal, and VCW≥7mm or EROA≥40mm^2 Symptomatic despite medical therapy; patient must be on diuretic therapy. Peak central venous pressure of ≥ 15mmHg The local site Heart Team determines that the patient is appropriate for transcatheter tricuspid intervention Patient is willing and able to comply with all specified study evaluations. Patient has NYHA functional classification of III or IV Patient is not eligible for standard-of-care surgical or interventional therapy assessed by the central heart team or has refused standard-of-care surgical and interventional therapy or has received standard-of-care TR therapy and remains symptomatic Patient understands the nature of the study and study requirements and is willing to provide written Informed Consent prior to any study-specific procedures. Exclusion Criteria: Patients will be excluded from participation if ANY of the following criteria apply: Echocardiographic parameters (Any of the following): I. LVEF < 20% II. Evidence of severe right ventricular dysfunction (e.g. right ventricular TAPSE < 13.0mm) III. IVC or SVC anatomy that precludes proper device deployment and function Systolic Pulmonary Artery Pressure > 70mmHg Severe aortic, mitral, and/or pulmonic valve stenosis and/or regurgitation Active endocarditis within 90 days of the scheduled implant Significant pericardial effusion Intra-cardiac masses, thrombi, or vegetation Thrombosis of the venous system Space-consuming lesion in the heart or on the valves, thrombus, or microbial colonization of the valves Untreated clinically significant coronary artery disease requiring immediate revascularization MI or known unstable angina within 30 days prior to the index procedure Any therapeutic invasive cardiac procedure within 30 days prior to the index procedure Any prior cardiac surgery, within 3 months of the index procedure Hemodynamic instability or treated with IV inotropes within 30 days of the index procedure Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mm Hg) Severe uncontrolled hypotension (SBP≤80 mmHg and/or DBP≤40 mmHg) Cerebrovascular Accident (CVA) within the past 90 days Kidney dysfunction with estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73 m^2 or patient is on chronic dialysis Significant frailty (i.e. Clinical Frailty Scale© (CFS) ≥ 7) within 90 days of the scheduled implant procedure Chronic liver disease with a MELD score of 20 or greater Chronic anemia (Hb < 9 g/L) not corrected by transfusion Thrombocytopenia (Platelet count< 100,000/mm3) or thrombocytosis (Platelet count > 750,000/mm3) Bleeding disorders or hypercoagulable state Active peptic ulcer or active gastrointestinal (GI) bleeding within 90 days of the scheduled implant Contraindication to anticoagulants or antiplatelet agents Currently or history of IV drug use Pregnant or lactating; or female of childbearing potential with a positive pregnancy test 24 hours before any study-related radiation exposure. Inability to access the femoral vein with a 24 FR guide (e.g., DVT, occluded femoral veins). Known allergy to stainless steel, nickel, titanium, PET or contrast agents that cannot be adequately pre-medicated. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically Impaired judgment Undergoing emergent or urgent treatment for tricuspid insufficiency Currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this study Co-morbid condition(s) that, in the opinion of the Investigator, limit life expectancy to < 12 months Cardiac cachexia In the judgment of the Investigator, co-morbid condition(s) that could limit the patient's ability to participate in the study, including compliance with follow-up requirements, or that could impact the scientific integrity of the study Patient is under guardianship Presence of any prosthetic device in the SVC or IVC (excluding pace-maker, ICD and CRT leads) Elevated inflammatory markers within 2 weeks of the scheduled procedure (e.g. CRP>1.5mg/dL).

Ages Eligible for Study
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Minimum Age: 40 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
Intervention Model: Single Group Assignment
Interventional Model Description: First In Human study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Innoventric Trillium™ Stent Graft Single Arm<br>Single-arm, open label, multi-center study | Device: Trillium™<br>* Trillium™ Stent Graft for Functional Tricuspid Valve Replacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint | Rate of device or procedure-related MAEs and Freedom from unplanned surgery or re-intervention, due to life-threatening device or procedure failure | Evaluated immediately after intervention, discharge and 30 days | 
| Technical performance | Successful access, delivery, and retrieval of the Trillium delivery system, the device is anchored both in SVC and IVC. | Evaluated immediately after intervention | 
| Efficacy Endpoint | TR grade as measured on the device valves (Echocardiography), or by hepatic vein systolic backflow (Echocardiography), or reduction in peak central venous pressure (Invasive hemodynamic measurement). | Evaluated immediately after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint | Composite of all device or procedure-related MAEs. | Assessment at 3-month, 6-month and 1-year | 
| Efficacy Endpoint | One or more of the following- TR grade measured on the device valves (Echocardiography), or by hepatic vein systolic backflow (Echocardiography), or measured by a regurgitant fraction (CMR) [at 30 days, 3-month, 6-month, and 1-year] Rate of hospitalizations for HF [at 30 days, 3-month, 6-month, and 1-year] Or one or more of the following- Clinical Frailty Scale (CFS) [at 30 days, 3-month, 6-month, and 1-year] HF functional class (NYHA) [at 30 days, 3-month, 6-month, and 1-year] Six-minute walk test (6MWT) [at 30 days, 3-month, 6-month, and 1-year] The Kansas City Cardiomyopathy Questionnaire (KCCQ) [at 30 days, 3-month, 6-month, and 1-year] | Assessment at 30 days, 3-month, 6-month and 1-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tricuspid Valve, Tricuspid Valve Insufficiency, Tricuspid Regurgitation