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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tricuspid Regurgitation
• Intervention / Treatment: Device: Trillium™

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • OLVZ Aalst
  • Antwerp, Belgium
    • ZNA
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Heart & Diabetes Center NRW
  • Berlin, Germany
    • Herzzentrum der Charité (DHZC)
  • Leipzig, Germany
    • Leipzig Heart Center
• Israel
  • Petah tikva, Israel, 4941492
    • Rabin Medical Center
• Spain
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro, Hospital Universitario de Vigo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Enrolled patients must meet ALL the following criteria:

1. Age >40 (no upper limit)
2. 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
3. Symptomatic despite medical therapy; patient must be on diuretic therapy.
4. Peak central venous pressure of ≥ 15mmHg
5. The local site Heart Team determines that the patient is appropriate for transcatheter tricuspid intervention
6. Patient is willing and able to comply with all specified study evaluations.
7. Patient has NYHA functional classification of III or IV
8. 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
9. 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:

1. 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

2. Systolic Pulmonary Artery Pressure > 70mmHg
3. Severe aortic, mitral, and/or pulmonic valve stenosis and/or regurgitation
4. Active endocarditis within 90 days of the scheduled implant
5. Significant pericardial effusion
6. Intra-cardiac masses, thrombi, or vegetation
7. Thrombosis of the venous system
8. Space-consuming lesion in the heart or on the valves, thrombus, or microbial colonization of the valves
9. Untreated clinically significant coronary artery disease requiring immediate revascularization
10. MI or known unstable angina within 30 days prior to the index procedure
11. Any therapeutic invasive cardiac procedure within 30 days prior to the index procedure
12. Any prior cardiac surgery, within 3 months of the index procedure
13. Hemodynamic instability or treated with IV inotropes within 30 days of the index procedure
14. Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mm Hg)
15. Severe uncontrolled hypotension (SBP≤80 mmHg and/or DBP≤40 mmHg)
16. Cerebrovascular Accident (CVA) within the past 90 days
17. Kidney dysfunction with estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73 m^2 or patient is on chronic dialysis
18. Significant frailty (i.e. Clinical Frailty Scale© (CFS) ≥ 7) within 90 days of the scheduled implant procedure
19. Chronic liver disease with a MELD score of 20 or greater
20. Chronic anemia (Hb < 9 g/L) not corrected by transfusion
21. Thrombocytopenia (Platelet count< 100,000/mm3) or thrombocytosis (Platelet count > 750,000/mm3)
22. Bleeding disorders or hypercoagulable state
23. Active peptic ulcer or active gastrointestinal (GI) bleeding within 90 days of the scheduled implant
24. Contraindication to anticoagulants or antiplatelet agents
25. Currently or history of IV drug use
26. Pregnant or lactating; or female of childbearing potential with a positive pregnancy test 24 hours before any study-related radiation exposure.
27. Inability to access the femoral vein with a 24 FR guide (e.g., DVT, occluded femoral veins).
28. Known allergy to stainless steel, nickel, titanium, PET or contrast agents that cannot be adequately pre-medicated.
29. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically
30. Impaired judgment
31. Undergoing emergent or urgent treatment for tricuspid insufficiency
32. 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
33. Co-morbid condition(s) that, in the opinion of the Investigator, limit life expectancy to < 12 months
34. Cardiac cachexia
35. 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
36. Patient is under guardianship
37. Presence of any prosthetic device in the SVC or IVC (excluding pace-maker, ICD and CRT leads)
38. Elevated inflammatory markers within 2 weeks of the scheduled procedure (e.g. CRP>1.5mg/dL).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Endpoints	transthoracic echocardiography (TTE) will be performed to determine acceptable performance of the device defined as a reduction in hepatic vein systolic backflow to moderate (systolic blunting) or better. In addition, the tricuspid valve complex will be imaged to capture the following parameters for comparison to baseline: Page 46 of 118 -Confidential-; TR grade (qualitative); Jet area; EROA and regurgitant volume; RV and LV dimensions; RA area/volume; LVEF; Tricuspid annular plane systolic excursion (TAPSE); IVC dimensions/respiratory variations; Pulmonary artery pressure (PAP); Right atrial pressure (RAP); RV pressure; IVC/SVC pressure It should be noted that the above-mentioned parameters are primarily being captured for research purposes and may not be affected by the device. The following clinical and laboratory parameters will be captured for comparison to baseline values: Mini Nutrition Assessment (MNA)®; Clinical Frailty Scale©	Assessment at 30 days, 3-month, 6-month and 1-year

Collaborators and Investigators

• Sponsor: Innoventric LTD

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): July 21, 2023
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Tricuspid Valve Insufficiency; Tricuspid Regurgitation; Tricuspid Valve
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Tricuspid Valve Insufficiency
• Other Study ID Numbers: CLD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No