A Study to Evaluate the Safety and Performance of LuX-Valve Plus System for Tricuspid Replacement

Study Overview
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Brief Summary
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This is a prospective, single-arm, multi-center trial to evaluate the LuX-Valve Plus system for treating symptomatic severe or greater TR in patients who are deemed high risk for tricuspid surgery. Treatment with the LuX-Valve Plus system may enable patients with tricuspid regurgitation to have a complete tricuspid valve replacement with a minimally invasive approach. A total of 93 subjects will be enrolled at up to 20 institutions worldwide. No single institution will be allowed to register more than 25% of total subjects. There is no minimum number of subjects to be registered at any site. Up to an additional 42 roll-in subjects, up to 3 per site, may be enrolled by operators without prior experience with the LuX-Valve Plus system to gain hands-on experience. The data of roll-in subjects will not count towards the overall enrollment cap. Safety and effectiveness results of roll-in subjects will be reported separately. All subjects will be evaluated at baseline, discharge, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years post-procedure

Official Title
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TRIal to Evaluate TraNsvenous TrIcuspid Valve ReplacemenT With LuX-Valve Plus System in Patients With Severe or Greater Tricuspid Regurgitation -- SafetY and Clinical Performance

Conditions
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Tricuspid Regurgitation

Intervention / Treatment
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* Device: Transcatheter Tricuspid Valve Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥50 years at time of consent Severe or greater TR (≥3+) assessed on transthoracic echocardiography by Echo Core Lab (ECL) using a 5-grade classification New York Heart Association (NYHA) Class III or IV In the judgment of the Site Heart Team, the subject has been adequately treated per applicable standards, including optimal medical therapy with diuretics The Site Heart Team determined that the subject is appropriate for transcatheter tricuspid valve replacement, and the subject is at high risk for tricuspid valve surgery Subject must provide written informed consent prior to any trial related procedure Exclusion Criteria: Systolic pulmonary artery pressure (sPAP) > 60 mmHg assessed by echocardiography Left Ventricular Ejection Fraction (LVEF) <40% Evidence of intracardiac mass, thrombus or vegetation Anatomical structures precluding proper device deployment or device vascular access, evaluated by echo or CT Ebstein Anomaly or congenital right ventricular dysplasia Surgical correction is indicated for other concomitant valvular disease (e.g., severe aortic, mitral and/or pulmonic valve stenosis and/or regurgitation) Subjects with concomitant valvular disease may treat their respective valve first, and wait 2 months before being reassessed for the trial. Pre-existing prosthetic valve(s) with clinically significant prosthetic dysfunction Sepsis or active endocarditis within 3 months, or infections requiring antibiotic therapy within 2 weeks prior to the planned procedure Untreated clinically significant coronary artery disease requiring revascularization Acute myocardial infarction or unstable ischemia-related angina within prior 30 days Any percutaneous coronary, intracardiac or carotid intervention within 30 days Cerebrovascular stroke (ischemic or bleeding) within prior 3 months to enrollment Active peptic ulcer or active gastrointestinal (GI) bleeding within prior 3 months to enrollment Inability to tolerate anticoagulation or antiplatelet therapy Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy at the time of screening Chronic liver failure or cirrhosis with MELD-Albumin Score ≥ 12 Severe lung disease or patient dependent on home oxygen and deemed unsuitable by the local heart team or eligibility committee for the study. Futility with estimated life expectancy<12 months. Subjects currently participating in another clinical trial of an investigational drug or device that has not yet completed its primary endpoint.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LuX-Valve Plus transvenous tricuspid valve and delivery system（LuX-Valve Plus System）<br>The LuX-Valve Plus System is intended for the treatment of patients with severe TR who are determined by a Heart Team to be at high risk of traditional open-heart surgery. | Device: Transcatheter Tricuspid Valve Intervention<br>* Due to unsustainable effect of medical therapy and high risks of surgical treatment, transcatheter tricuspid valve intervention (TTVI) has been a major field of study in the world in the last 10 years. TTVI could potentially reduce TR with lower periprocedural risk and improve the patient's clinical status and prognosis. Per the ESC guidelines for surgical and interventional treatment of tricuspid regurgitation (2021 ESC/EACTS Guidelines for the Management of Valvular Heart Disease), Transcatheter intervention for symptomatic secondary severe TR may be considered in inoperable patients at a Heart Valve Centre with expertise in the treatment of tricuspid valve disease (Class IIb). 20 Transcatheter tricuspid treatment options can be divided into categories based on their mechanism of action: coaptation enhancement (edge-to-edge repair and spacer device), annuloplasty devices, caval valve implantation and valve replacement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite endpoint of Major Adverse Event (MAE) at 30 days post procedure | A composite endpoint of Major Adverse Event (MAE) at 30 days post procedure, as listed below: Cardiovascular Mortality Myocardial Infarction (MI) Stroke New onset renal failure requiring unplanned dialysis or renal replacement therapy Severe Bleeding (includes fatal, life-threatening and extensive bleeding as defined by MVARC) Non-selective tricuspid valve surgery or transcatheter re-intervention post procedure Major cardiac structural complications Major access site and vascular complications New pacemaker implantation due to AV block | 30 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Secondary Endpoints-Device Success Rate | Device success is defined as successful deployment of the device and removal of the delivery system as planned, with no unplanned surgery related to the device or access procedure. | From the first skin incision for the investigational device to the time patient's exist from OR/Cath lab,assessed up to 24 hours post procedure. | 
| Acute Secondary Endpoints-Procedural Success Rate | Device success without clinically significant PVL, as determined by the Echo Core Lab (ECL) assessment of a discharge TTE. Subjects who die or undergo tricuspid valve surgery before discharge are procedure failures. | 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure | 
| Acute Secondary Endpoints-Clinical Success Rate at 30 days | Procedural success without MAEs at 30 days. | at 30 days | 
| Clinical and Functional Endpoints-All-cause mortality | All-cause mortality | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Cardiovascular mortality | Cardiovascular mortality | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Heart failure hospitalization | Heart failure hospitalization | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Tricuspid valve surgery or transcatheter re-intervention | Tricuspid valve surgery or transcatheter re-intervention | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-NYHA Functional Class | NYHA Functional Class | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Distance of 6-Minute Walk Test (6MWT) | Distance of 6-Minute Walk Test (6MWT) | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Kansas City Cardiomyopathy Questionnaire (KCCQ) | Kansas City Cardiomyopathy Questionnaire (KCCQ)：Scores are transformed to a range of 0-100,in which higher scores reflect better health status. | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Clinical and Functional Endpoints-Edema assessment | Edema assessment (1+ to 4+) | at 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-TR Severity Grade | TR Severity Grade | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Vena Contracta Width | Vena Contracta Width | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Regurgitation Jet Area | Regurgitation Jet Area | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Effective Regurgitant Orifice Area (EROA) | Effective Regurgitant Orifice Area (EROA) | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Regurgitant Volume | Regurgitant Volume | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Mean Tricuspid valve inflow gradient | Mean Tricuspid valve inflow gradient | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right Atrial Volume | Right Atrial Volume | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right ventricular functions assessments:TAPSE | Right ventricular functions assessments:TAPSE | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right ventricular functions assessments:fractional area change（FAC） | Right ventricular functions assessments:fractional area change（FAC） | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right ventricular functions assessments:systolic tricuspid lateral annular tissue velocity S' | Right ventricular functions assessments:systolic tricuspid lateral annular tissue velocity S' | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right ventricular functions assessments:Hepatic vein flow reversal | Right ventricular functions assessments:Hepatic vein flow reversal | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Right ventricular functions assessments:Inferior Cava Vein Diameter/respiratory variations | Right ventricular functions assessments:Inferior Cava Vein Diameter/respiratory variations | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Systolic pulmonary artery pressure | Systolic pulmonary artery pressure | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Cardiac Output | Cardiac Output | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Left Ventricular Ejection Fraction (LVEF) | Left Ventricular Ejection Fraction (LVEF) | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure | 
| Echocardiographic Endpoints-Paravalvular leak severity | Paravalvular leak severity | at baseline, 7-day post procedure, or at discharge if the subjects are discharged within 7 days after the procedure, 30 days, 6 months, 12 months and annually until 5 years post-procedure |