TRIcvalve biCAVal Valve System for Severe Tricuspid Regurgitation Regurgitation (TRICAV)

Study Overview
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Brief Summary
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The TricValve® Transcatheter Bicaval Valve System is a bicaval transcatheter tricuspid valve implantation system, which includes the TricValve® Transcatheter Bicaval Valve for superior vena cava (SVC) and the TricValve® Transcatheter Bicaval Valve for inferior vena cava (IVC). The TricValve® Transcatheter Bicaval Valves are pre-mounted into the TricValve® Delivery System which is used for percutaneous access and delivery of the TricValve® Transcatheter Bicaval Valve in the vena cava. The system is a single use, sterile device compatible with all the valve sizes. The prostheses are implanted percutaneously into the inferior and superior vena cava without disturbing the native tricuspid valve. The device is made of bovine pericardium leaflets sutured on a nitinol self-expanding stent system.

Detailed Description
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This is a prospective multicenter clinical investigation designed to evaluate the safety and effectiveness of the TricValve® Transcatheter Bicaval Valve System for improving outcomes in symptomatic subjects with severe TR deemed by the local Heart Team to be at high risk for tricuspid valve surgery. Patients who meet all of the study inclusion criteria, will be treated with the TricValve. After the intervention, patients will be followed up closely for 12 months. Long term safety and efficacy data will be collected annually up to 5 years.

Official Title
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Prospective, Multicenter, Randomized, Controlled Clinical Trial of the TricValve® Transcatheter Bicaval Valve System in Subjects With Severe Symptomatic Tricuspid Regurgitation (TR) - TRICAV Trial

Conditions
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Tricuspid Regurgitation, Tricuspid Valve Disease

Intervention / Treatment
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* Device: TricValve® Transcatheter Bicaval Valve System
* Procedure: Medical Therapy Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be 18 years or older, at the time of signing the informed consent. Subjects must have severe TR. TR severity is determined by the assessment of a qualifying transthoracic echocardiogram (TTE) confirmed by an echocardiography Core Lab. The Core Lab may request a trans-esophageal echocardiogram (TEE) or cardiac magnetic resonance imaging (CMR). Subject has been optimally medically managed for heart failure per applicable standards and stable for at least 30 days. The site Heart Team (consisting of 1 Interventional Cardiologist, 1 Cardiac Surgeon, 1 Imaging Cardiologist, 1 Heart Failure Specialist) and the Independent Eligibility Committee (IEC) judges the subject to be high risk for tricuspid valve surgery. Inclusion is limited to subjects with severe symptomatic TR who are not candidates for approved transcatheter tricuspid valve device. NYHA Class 3-4 (not on inotropes) OR HF admission in the past 6 months. Significant IVC and/or SVC backflow on echocardiography, and vwave ≥20mmHg on right heart catheterization (measured in IVC and or SVC 2-4cm above/below the RA inflow). Anatomically suitable for the TricValve Device per CT and right heart catheterization. Exclusion Criteria: Requirement of another planned cardiac procedure (i.e., PCI) up to 30 days pre- or post- procedure Left Ventricular Ejection Fraction (LVEF) ≤30% on echocardiography Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation Invasive pulmonary artery systolic pressure >65 mmHg Recent Cerebrovascular Accident (CVA) (within 3 months) Need for left-sided or pulmonary valve treatment within 60 days of screening Tricuspid stenosis Thrombosis of lower extremity veins or presence of an IVC filter Unable to take Coumadin or Direct Oral Anticoagulants (DOAC)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multicenter, randomized controlled clinical trial. Subjects will be selected by their local Heart Team to be at high risk for tricuspid valve repair or replacement and deemed eligible by an independent eligibility committee (IEC). Subjects will be randomized in a 1:1 ratio to receive either: TricValve® Device (Device) Group: subjects will undergo TricValve® implantation and will continue to be managed with optimal medical therapies, per physician discretion Or Control Arm Treatment Group: subjects will continue to be managed on local standard of care (SOC) therapy for severe TR per physician discretion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TricValve® Device (Device) Group<br>subjects will undergo TricValve® implantation and will continue to be managed with optimal medical therapies, per physician discretion. | Device: TricValve® Transcatheter Bicaval Valve System<br>* The TricValve® Transcatheter Bicaval Valve System is a bicaval transcatheter tricuspid valve implantation system, which includes the TricValve® Transcatheter Bicaval Valve for superior vena cava (SVC) and the TricValve® Transcatheter Bicaval Valve for inferior vena cava (IVC). The system is a single use, sterile device compatible with all the valve sizes. The valves are premounted in the TricValve® Delivery System. The prostheses are implanted percutaneously into the inferior and superior vena cava without disturbing the native tricuspid valve. The device is made of bovine pericardium leaflets sutured on a nitinol self-expanding stent system available in sizes 25 and 29 for superior vena cava and 31 and 35 for inferior vena cava. The valve is implanted percutaneously by the transfemoral approach. The valves are supplied already premounted into the TricValve® Delivery System.<br>* Other names: TricValve;|
| Placebo Comparator: Control Arm Treatment Group<br>subjects will continue to be managed on local standard of care (SOC) therapy for severe TR per physician discretion. | Procedure: Medical Therapy Arm<br>* Subjects will be randomized and managed on standard of care therapy, per physician discretion. *Ability to cross-over after 18-Month Follow-Up completed<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Number of days until death | 1 Month and 12 Months | 
| Stroke | Number of days until death | 1 Month | 
| Pulmonary Embolism | Number of days until death | 1 Month | 
| Valve Academic Research Consortium (VARC) type 2-4 bleeding complication | Number of days until death | 1 Month | 
| Major vascular, access-related, or cardiac structural complication | Number of days until death | 1 Month | 
| Stage 3 Acute Kidney Injury with increase in serum creatinine >300% (>3.0x increase) and/or serum creatinine ≥4.0mg/dL (≥354 μmol/L) with an acute increase of ≥ 0.5 mg/dL (≥44 μmol/L) | Number of days from baseline until increase | 7 Days | 
| Stage 4 Acute Kidney Injury requiring new temporary or permanent renal replacement therapy | Number of days until new renal replacement therapy | 1 Month | 
| Emergency surgery or intervention related to the device/procedure complications | Number of days until emergency surgery or intervention | 1 Month | 
| Right Ventricular Assist Device (RVAD) implantation or heart transplant | Number of days until Right Ventricular Assist Device (RVAD) implantation or heart transplant | 12 Months | 
| Tricuspid valve surgery or percutaneous tricuspid intervention | Number of days until tricuspid valve surgery or percutaneous tricuspid intervention | 12 Months | 
| Heart Failure Events | Number of heart failure episodes including hospitalization, or worsening heart failure | 12 Months | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Score | Change in KCC score (score ranges between 0 and 100) | 12 Months | 
| New York Heart Association (NYHA class) | Change in NYHA class (range from I to IV) | 12 Months | 
| Six Minute Walking Test (6MWT) | Change in walking distance | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success of device placement (at exit from procedure room) | Freedom from mortality Successful access, delivery of the device, and retrieval of the delivery system Correct positioning of the device into the proper anatomical location Freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication | Intraprocedural | 
| Device success within 30 days after device placement | Technical success Freedom from mortality Freedom from surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication | 1 Month | 
| Procedural success (at 30 days) | All of the following criteria must be met to be considered a procedural success: Device success (defined above), and Absence of major device or procedure related serious adverse events | 1 Month | 
| Mortality | Number of days until death | 18 Months | 
| RVAD implantation or heart transplant | Number of days until Right Ventricular Assist Device (RVAD) implantation or heart transplant | 18 Months | 
| Tricuspid valve surgery or percutaneous tricuspid intervention | Number of days until tricuspid valve surgery or percutaneous tricuspid intervention | 18 Months | 
| Heart Failure hospitalization or worsening Heart Failure (HF) which encompasses treatment with IV diuretics in the office or Emergency Department treatment during a <24-hour time period | Number of days until Heart Failure hospitalization or worsening Heart Failure | 18 Months | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Score | Change in KCCQ score (score ranges between 0 and 100) | 6 and 18 Months and annually up to 5 years | 
| New York Heart Association (NYHA class) | Change in NYHA class (range from I to IV) | 6 and 18 Months and annually up to 5 years | 
| Six Minute Walking Test (6MWT) | Change in walking distance | 6 and 18 Months and annually up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Tricuspid Regurgitation