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

Tricuspid Regurgitation Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04289870
• Other study ID #: CLD-001
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 24, 2020
• Est. completion date: June 2026

Study information

• Verified date: December 2023
• Source: Innoventric LTD
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: June 2026
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Tricuspid Regurgitation
• Tricuspid Valve Insufficiency

Intervention

Device:
• Trillium™
Trillium™ Stent Graft for Functional Tricuspid Valve Replacement

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Innoventric LTD

Countries where clinical trial is conducted

Belgium,  Germany,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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
Primary	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	Safety Endpoint	Composite of all device or procedure-related MAEs.	Assessment at 3-month, 6-month and 1-year
Secondary	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