A Prospective, Randomized Multicenter Clinical Trial of the TricValve® Transcatheter Bicaval Valve System in Subjects With Severe Tricuspid Regurgitation.

A Prospective, Randomized Multicenter Clinical Trial of the TricValve® Transcatheter Bicaval Valve System in Subjects With Severe Tricuspid Regurgitation.

Pivotal trial to evaluate the safety and effectiveness of the P&F TricValve® Transcatheter Bicaval Valve System.

The study is a prospective, multi-center, randomized controlled pivotal clinical trial to evaluate the safety and effectiveness of the TricValve System with optimal medical therapy (OMT) compared to OMT alone in the treatment of patients with severe tricuspid regurgitation and unsuitable for approved transcatheter therapies. Subjects will be followed at discharge, 1 month, 30 days, 3 months, 6 months 12 months, and annually up to 5 years.

Eligibility Criteria for Randomized Cohort:

Inclusion Criteria:

1. Age between 18 years and 85 years old, at the time of signing the informed consent.
2. Severe tricuspid regurgitation (TR) and Caval Reflux (CR), as determined by the qualifying transthoracic echocardiogram (TTE) confirmed by an echocardiography Core Lab. TVARC criteria will be used for the definition of TR severity.
3. NYHA Class II-III-IVa (not on inotropes, IABP or LVAD) or heart failure (HF) admission in the past 6 months.
4. Adequately treated with optimal medical therapy (OMT) for heart failure per the local Heart Team at the time of TR assessment for eligibility (TTE). OMT includes stable oral diuretic medications.
5. High risk for open surgery and is appropriate for transcatheter tricuspid therapies according to the local heart team.
6. Patient is unsuitable for approved transcatheter therapies and is eligible for the TricValve procedure, based on review of screening/baseline data and imaging core lab measurements by Central Screening Committee.
7. For females of childbearing potential, negative pregnancy test.
8. Capable and willing to provide signed informed consent

Exclusion Criteria:

CONCOMITANT PROCEDURES

1. Patient had a recent MI, stroke, or cardiovascular accident; underwent coronary artery bypass graft surgery, had a percutaneous coronary intervention or other major cardiovascular surgery within 90 days prior to TricValve implantation.

2. Patient requires another planned major cardiac procedure, including left-sided transcatheter intervention or surgery (e.g. severe aortic stenosis, severe mitral regurgitation), coronary artery bypass or PCI or pulmonary valve correction.

   CARDIOVASCULAR CONDITIONS

3. LVEF ≤ 30% on echocardiography.

4. Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation.

5. Severe right ventricular dysfunction.

6. Cardiac amyloidosis.

7. Pulmonary artery systolic pressure (PASP) >65 mmHg assessed with Echo Doppler and /or right heart catheterization.

8. Lower extremity venous thrombosis and/or the presence of an IVC filter at the time of or 6 months prior to the TricValve procedure.

9. Hemodynamically significant pericardial effusion.

10. Hemodynamic instability, cardiogenic shock, inotropic support, intra-aortic balloon pump or acute heart failure within 30 days prior to the TricValve procedure.

11. Patient with refractory heart failure requiring advanced intervention (i.e. left ventricular assist device, transplantation) (ACC/ AHA/ ESC/ EACTS Stage D heart failure).

12. Presence of significant congenital or acquired heart disease such as RV dysplasia, arrhythmogenic RV or other conditions that could interfere with the TricValve procedure.

    ALLERGIES / INTOLERANCE

13. Any known allergy or hypersensitivity to nitinol, bovine tissue, or contrast media that cannot be adequately treated with pre-medication.

14. Unable to tolerate anticoagulation/antiplatelet therapy

    COMORBIDITIES

15. Any known life-threatening condition with an estimated life span of less than 12 months.

16. Platelet count < 75,000/mm3

17. Child-Pugh Severity Class C (10-15 points).

18. Severe renal insufficiency with estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 or requiring chronic renal replacement therapy at the time of enrollment.

19. Endocarditis or active/ongoing infection requiring antibiotics.

20. Unable to walk at least 100 meters in a 6-minute walk test.

21. Known bleeding or clotting disorders or patient refuses blood transfusion.

22. Active gastrointestinal (GI) bleeding within 3 months of TricValve procedure.

23. Prior Malignancy: this study excludes participants at material risk of near-term cancer-related morbidity/mortality that could confound 12-month outcomes. This study allows the inclusion of fully treated, remote malignancies with documented No Evidence of Disease (NED)" criteria

    a. History of any malignancy within 5 years prior to randomization or any active malignancy, except: i. Adequately treated non-melanoma skin cancer (basal or squamous cell) with no evidence of disease, or ii. Carcinoma in situ (e.g., cervical, breast DCIS) treated with curative intent and no evidence of disease.

    b. Participants with a prior malignancy diagnosed >5 years before randomization are eligible if they meet all of the "No Evidence of Disease (NED)" criteria as specified below: i. No signs/symptoms of cancer on history and physical exam per standard of care; ii. No radiologic evidence of disease on surveillance imaging if such imaging is routinely indicated for that tumor type (not protocol-mandated); iii. Tumor markers (if applicable for that cancer) not suggestive of recurrence (e.g., stable/undetectable within site's lab reference and oncologist's judgment); iv. No active anti-cancer therapy (cytotoxic chemotherapy, immunotherapy, targeted therapy, radiotherapy) and none planned; v. Treating oncologist's attestation (or primary physician if oncology follow-up is complete) that the participant is disease-free and appropriate for participation.

    GENERAL EXCLUSIONS

24. Use or participation in other investigational device or drug study in which the patient has not reached a primary endpoint to treat cardiovascular conditions related to the outcomes of the current study.

25. Any other condition that would preclude the ability to meet study requirements in the opinion of the investigator.

26. Psychiatric/behavioral issues or other medical or social conditions that preclude valid consent and follow-up

27. Pregnant or breastfeeding subjects and those who plan pregnancy during the clinical investigation follow-up period.

Eligibility Criteria for Single Arm Cohort:

Inclusion Criteria:

1. Age > 85 years.
2. NYHA Class III-IV, on intravenous inotropes, IABP or LVAD.
3. LVEF ≤ 30% on echocardiography.
4. Severe RV dysfunction.
5. Severe pulmonary hypertension (PH), defined as Pulmonary artery systolic pressure (PASP) >65 mmHg assessed with Echo Doppler and /or mean Pulmonary Artery Pressure (mPAP >35) by right heart catheterization.
6. Renal insufficiency: eGFR between 25 and 30 mL/min/ 1.73 m² or on chronic renal replacement therapy.
7. Patient unable to walk a minimum distance of 100 mt during 6 minute walk test.
8. Prior malignancy not meeting the requirements applied for the Randomized Cohort, specified in Exclusion Criterion #23.
9. Comorbidities precluding inclusion in the Randomized Cohort (exclusion criteria #15 to #24).