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

Overview

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

Detailed description

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.

Interventions

• Device TricValve System
  • Heterotopic Transcatheter Valve Replacement (TVR) with the TricValve System in conjunction with optimal medical therapy
• Drug Optimal medical therapy
  Optimal medical therapy

Primary outcome measures

• Randomized Cohort: Caval Reflux (CR) grade reduction [Time frame: 6 months]
• Randomized Cohort: Hierarchical composite endpoint including: Kansas City Cardiomyopathy Questionnaire (KCCQ) improvement, New York Heart Association (NYHA) functional class improvement, and 6-minute walk test distance improvement [Time frame: 6 months]
• Randomized Cohort: Rate of Major Adverse Events (MAE) [Time frame: 30 days]
• Randomized Cohort: Hierarchical composite endpoint: all-cause mortality, RVAD implantation or heart transplant, tricuspid valve surgery or percutaneous tricuspid intervention, heart failure hospitalizations, KCCQ improvement, NYHA functional class improv [Time frame: 1 year]
• Registry Cohort: Rate of Major Adverse Events (MAE) [Time frame: 30 days]

Secondary outcome measures (12)

• Randomized Cohort: Percentage of Device- and/or Procedure-related MAEs [Time frame: 1 year]
• Randomized Cohort: All-Cause mortality and Cardiovascular Mortality [Time frame: 6 months and 1 year]
• Randomized Cohort: Heart Failure Hospitalizations (HFH) [Time frame: 6 months and 1 year]
• Randomized Cohort: RVAD Implantation or Heart Transplant [Time frame: 6 months and 1 year]
• Randomized Cohort: Atrial Fibrillation [Time frame: 1 year]
• Randomized Cohort: Quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) . [Time frame: 6 months and 1 year]
• Randomized Cohort: Changes in symptom status New York Heart Association (NYHA class) [Time frame: 6 months and 1 year]
• Randomized Cohort: Changes in functional capacity (6-minute walk test, 6MWT). [Time frame: 6 months and 1 year]
• Registry Cohort: Heart Failure Hospitalization [Time frame: 1 year]
• Registry Cohort: Changes in Quality of life (by Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score). [Time frame: 1 year]
• Roll-In Cohort: Percentage of Device- and/or Procedure-related MAEs [Time frame: 1 year]
• Roll-In Cohort: All-Cause mortality and Cardiovascular Mortality [Time frame: 6 months and 1 year]

Eligibility criteria

Eligibility Criteria for Randomized Cohort:

Inclusion criteria

• Age between 18 years and 85 years old, at the time of signing the informed consent.
• 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.
• NYHA Class II-III-IVa (not on inotropes, IABP or LVAD) or heart failure (HF) admission in the past 6 months.
• 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.
• High risk for open surgery and is appropriate for transcatheter tricuspid therapies according to the local heart team.
• 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.
• For females of childbearing potential, negative pregnancy test.
• Capable and willing to provide signed informed consent

Exclusion criteria

CONCOMITANT PROCEDURES

• 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.
• 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

• LVEF ≤ 30% on echocardiography.
• Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation.
• Severe right ventricular dysfunction.
• Cardiac amyloidosis.
• Pulmonary artery systolic pressure (PASP) >65 mmHg assessed with Echo Doppler and /or right heart catheterization.
• Lower extremity venous thrombosis and/or the presence of an IVC filter at the time of or 6 months prior to the TricValve procedure.
• Hemodynamically significant pericardial effusion.
• Hemodynamic instability, cardiogenic shock, inotropic support, intra-aortic balloon pump or acute heart failure within 30 days prior to the TricValve procedure.
• Patient with refractory heart failure requiring advanced intervention (i.e. left ventricular assist device, transplantation) (ACC/ AHA/ ESC/ EACTS Stage D heart failure).
• 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

• Any known allergy or hypersensitivity to nitinol, bovine tissue, or contrast media that cannot be adequately treated with pre-medication.
• Unable to tolerate anticoagulation/antiplatelet therapy

COMORBIDITIES

• Any known life-threatening condition with an estimated life span of less than 12 months.
• Platelet count < 75,000/mm3
• Child-Pugh Severity Class C (10-15 points).
• 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.
• Endocarditis or active/ongoing infection requiring antibiotics.
• Unable to walk at least 100 meters in a 6-minute walk test.
• Known bleeding or clotting disorders or patient refuses blood transfusion.
• Active gastrointestinal (GI) bleeding within 3 months of TricValve procedure.
• 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

• 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.
• Any other condition that would preclude the ability to meet study requirements in the opinion of the investigator.
• Psychiatric/behavioral issues or other medical or social conditions that preclude valid consent and follow-up
• Pregnant or breastfeeding subjects and those who plan pregnancy during the clinical investigation follow-up period.

Eligibility Criteria for Single Arm Cohort:

Inclusion criteria

• Age > 85 years.
• NYHA Class III-IV, on intravenous inotropes, IABP or LVAD.
• LVEF ≤ 30% on echocardiography.
• Severe RV dysfunction.
• 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.
• Renal insufficiency: eGFR between 25 and 30 mL/min/ 1.73 m² or on chronic renal replacement therapy.
• Patient unable to walk a minimum distance of 100 mt during 6 minute walk test.
• Prior malignancy not meeting the requirements applied for the Randomized Cohort, specified in Exclusion Criterion #23.
• Comorbidities precluding inclusion in the Randomized Cohort (exclusion criteria #15 to #24).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 34 centers

• University of Alabama — Birmingham
• St. Joseph's Hospital and Medical Center — Phoenix
• UC Davis Health — Sacramento
• Scripps Memorial Hospital La Jolla — San Diego
• UCSF — San Francisco
• Kaiser Permanente — San Jose
• MedStar Washington Hospital Center (MWHC) — Washington D.C.
• Delray Medical Center — Delray Beach
• … and 26 more centers

Publications

• Amat-Santos IJ, Estevez-Loureiro R, Sanchez-Recalde A, Cruz-Gonzalez I, Pascual I, Mascherbauer J, Abdul-Jawad Altisent O, Nombela-Franco L, Pan M, Trillo R, Moreno R, Delle Karth G, Blasco-Turrion S, Sanchez-Luna JP, Revilla-Orodoea A, Redondo A, Zamorano JL, Puri R, Iniguez-Romo A, San Roman A. Right heart remodelling after bicaval TricValve implantation in patients with severe tricuspid regurgi PMID 37083622
• Blasco-Turrion S, Briedis K, Estevez-Loureiro R, Sanchez-Recalde A, Cruz-Gonzalez I, Pascual I, Mascherbauer J, Abdul-Jawad Altisent O, Nombela-Franco L, Pan M, Trillo R, Moreno R, Delle Karth G, Sanchez-Luna JP, Gonzalez-Gutierrez JC, Revilla-Orodoea A, Zamorano JL, Gomez-Salvador I, Puri R, San Roman JA, Amat-Santos IJ. Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid PMID 38069986

Identifiers

NCT: NCT06458907 · CTP-TRIC-005-II

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗