TRI-REPAIR: TrIcuspid Regurgitation RePAIr With CaRdioband Transcatheter System

Study Overview
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Brief Summary
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The current management of tricuspid regurgitation (TR) is either conservative (by medication) or by surgery, usually in concomitant with other valves repair or replacement. TR can worsen or appear late after successful mitral valve surgery which portends a poor prognosis. However, standard surgical approaches requiring cardiopulmonary bypass and especially second surgery have an excessive risks. Thus many patients are denied surgery because of unfavorable risk-benefit balance. Therefore there is a need for novel devices enabling interventional cardiologists and cardiothoracic surgeons to perform tricuspid annuloplasty by transcatheter methods. Cardioband replicates established surgical techniques (e.g., annuloplasty) using transfemoral approach, without sutures and with adjusted on the beating heart. Similar to the approved indication for mitral annuloplasty. The Cardioband System is expected to allow for treatment of patients that would otherwise not undergo Tricuspid valve repair due to the invasiveness of current techniques.

Detailed Description
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The Cardioband Transcatheter System (Cardioband) is a marketed system that was approved for treatment of secondary (functional) mitral regurgitation (FMR) (CE granted on September 2015). The Cardioband is an annuloplasty band that is similar to a surgical annuloplasty, however deployed on the beating heart through a transvenous approach. The CE mark study with 30 subjects has been completed and documented significant reduction of severity of MR and improvement in quality of life by Minnesota living with heart failure questionnaire (MLHFQ), New York Heart Association (NYHA) and 6- minute walk test (6MWT), in subjects with moderate to severe MR. The aim of the current study is to evaluate the Cardioband annuloplasty system for repair the Tricuspid Regurgitation.

Official Title
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TRI-REPAIR: TrIcuspid Regurgitation RePAIr With CaRdioband Transcatheter System

Conditions
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Tricuspid Valve Insufficiency, Tricuspid Regurgitation, Tricuspid Valve Regurgitation, Cardiovascular Diseases, Heart Valve Diseases, Heart Diseases, Cardiac Valve Annuloplasty

Intervention / Treatment
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* Device: Cardioband Tricuspid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic functional tricuspid regurgitation (FTR) with annular diameter ≥ 40 mm with valve Systolic pulmonary pressure (sPAP) ≤ 60mmHg ≥18 years old New York Heart Association (NYHA) Class II-IVa Symptomatic despite Guideline Directed Medical Therapy (GDMT); at minimum patient on diuretic regimen LVEF ≥ 30% Patient is willing and able to comply with all specified study evaluations The Local Site Heart Team concur that surgery will not be offered as a treatment option Transfemoral access of the Cardioband is determined to be feasible Exclusion Criteria: Aortic, mitral and/or pulmonic valve stenosis and/or regurgitation ≥ moderate Severe uncontrolled hypertension (Systolic BP ≥ 180 mmHg and/or Diastolic BP ≥ 110 mm Hg) Previous tricuspid valve repair or replacement Trans-tricuspid pacemaker or defibrillator leads suggesting impingement of the of the tricuspid valve leaflets, as evaluated by echocardiography Active endocarditis MI or known unstable angina within the 30 days prior to the index procedure Any percutaneous coronary intervention (PCI) or transcatheter valvular intervention within 30 days prior to the index Hemodynamic instability or on IV inotropes Cerebrovascular Accident (CVA) within the past 6 months Subject is on chronic dialysis Anemia (Hb < 9 g/dL) not corrected by transfusion Bleeding disorders or hypercoaguable state Active peptic ulcer or active gastrointestinal (GI) bleeding Contraindication to anticoagulants Known allergy to stainless steel, nickel, and/or polyester Pregnant or lactating; or female of childbearing potential with a positive pregnancy test 24 hours before any study-related radiation exposure In the judgment of the Investigator, co-morbid condition(s) that could limit the subject's ability to participate in the study, including compliance with follow-up requirements, or that could impact the scientific integrity of the study Life expectancy of less than 12 months Impaired judgment and/or is undergoing emergency treatment 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 intra-cardiac masses, thrombi or vegetations Patients with cardiac cachexia Subjects in whom transesophageal echocardiography is contraindicated . Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically Untreated clinically significant CAD requiring revascularization Echocardiographic evidence of severe right ventricular dysfunction Any coronary or endovascular surgery, within 3 months prior to procedure

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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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 |
| --- | --- |
| Other: Cardioband Tricuspid procedure<br>Tricuspid valve repair with Cardioband implanted via transcatheter procedure under transesophageal echocardiography (TEE) and fluoroscopy guidance | Device: Cardioband Tricuspid<br>* The Cardioband Adjustable implant is delivered and anchored to the tricuspid valve annulus by a transfemoral delivery system. The Cardioband TR will be deployed and adjusted under trans-esophageal and fluoroscopy guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Serious Adverse Events (MSAEs) and Serious Adverse Device Effects (SADE) | Overall rate of Major Serious Adverse Events (MSAEs)* and serious adverse device effects (SADE) | 30 days | 
| Access, Deployment and Positioning of the Cardioband Device | Successful access, deployment and positioning of the Cardioband device | Intra-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical Success | Successful access, deployment and positioning of the Cardioband device and septolateral reduction. | 1, 6, 12, and 24 months | 
| Tricuspid Regurgitation [Paired Baseline and Follow-Up] | Data available at each time point was reported as number of patients with TR grades between Trace, Mild, Moderate, and Severe. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| Tricuspid Regurgitation [Full Analysis Data Set] | All data available at each time point was reported as number of patients with TR grades between Trace, Mild, Moderate, Severe. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| Effective Regurgitant Orifice Area (EROA) [Paired Baseline and Follow-Up] | Effective regurgitant orifice area (EROA) at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per core lab | 1, 6, 12, and 24 months over baseline | 
| Effective Regurgitant Orifice Area (EROA) [Full Analysis Data Set] | All data available for Effective regurgitant orifice area (EROA) at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| Regurgitant Volume [Paired Baseline and Follow-Up] | Regurgitant Volume (by Echocardiography) data available at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| Regurgitant Volume [Full Analysis Data Set] | All data for Regurgitant Volume (by Echocardiography) at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| TAPSE [Paired Baseline and Follow-Up] | Tricuspid Annular Plane Systolic Excursion at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per core lab. | 1, 6, 12, and 24 months over baseline | 
| TAPSE [Full Analysis Data Set] | All data for Tricuspid Annular Plane Systolic Excursion at 1 month, 6 months, 12 months, and 24 months over baseline. Data analyses based on core lab assessment. | 1, 6, 12, and 24 months over baseline | 
| NYHA [Paired Baseline and Follow-Up] | NYHA classification data available at 1 month, 6 months, 12 months, 24 months over baseline. Measure Description: NYHA Classification - The stages of heart failure: Class I - No symptoms and no limitation in ordinary physical activity Class II - Mild symptoms and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. | 1, 6, 12, and 24 months over baseline | 
| NYHA [Full Analysis Data Set] | All data available for NYHA classification at 1 month, 6 months, 12 months, and 24 months over baseline. Measure Description: NYHA Classification - The stages of heart failure: Class I - No symptoms and no limitation in ordinary physical activity Class II - Mild symptoms and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. | 1, 6, 12, and 24 months over baseline | 
| 6MWT [Paired Baseline and Follow-Up] | Distance in meters walked during 6 Minute Walk Test (6MWT) at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| 6MWT [Full Analysis Data Set] | Distance in meters walked during 6 minute walk test (6MWT) at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Kansas City Cardiomyopathy (KCCQ) [Paired Baseline and Follow-Up] | The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered, 12-item questionnaire that quantifies physical limitations, symptoms, self-sufficiency, social interaction and quality of life. Scores range from 0-100, in which higher scores reflect better health status. An increase in the KCCQ-12 score reflects an improvement in symptoms for the subject. A mean difference over time of 5 points on the KCCQ-12 summary score reflects a clinically significant change in heart failure status. | 1, 6, 12, and 24 months over baseline | 
| Kansas City Cardiomyopathy (KCCQ) [Full Analysis Data Set] | The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered, 12-item questionnaire that quantifies physical limitations, symptoms, self-sufficiency, social interaction and quality of life. Scores range from 0-100, in which higher scores reflect better health status. An increase in the KCCQ-12 score reflects an improvement in symptoms for the subject. A mean difference over time of 5 points on the KCCQ-12 summary score reflects a clinically significant change in heart failure status. | 1, 6, 12, and 24 months over baseline | 
| Left Ventricle Ejection Fraction (LVEF) [Paired Baseline and Follow-Up] | Left ventricle ejection fraction data available for 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis based on core lab assessment. | 1, 6, 12, and 24 months over baseline | 
| Left Ventricle Ejection Fraction (LVEF) [Full Analysis Data Set] | All available data for left ventricle ejection fraction at 1 month, 6 months, 12 months, and 24 months over baseline. Data analysis per echo core lab. | 1, 6, 12, and 24 months over baseline | 
| Left Ventricle End Diastolic Volume Index (LVEDVI) [Full Analysis Data Set] | Left ventricle end diastolic volume index data available for 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Left Ventricle End Systolic Volume Index (LVESVI) [Full Analysis Data Set] | Left ventricle end systolic volume index data available at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| NT-pro BNP [Full Analysis Data Set] | N-terminal prohormone of brain natriuretic peptide data available at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Diuretic Therapy | Diuretic Therapy data available at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Bilirubin [Full Analysis Data Set] | Bilirubin data available at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Blood Urea Nitrogen (BUN), Serum Creatinine [Full Analysis Data Set] | All available data for Blood urea nitrogen (BUN) and Serum Creatinine at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Activity by Wearable Device | Activity by wearable device available data at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Glutamic Oxaloacetic Transaminase (GOT) Aspartate Transaminase (AST) [Full Analysis Data Set] | All data available for Glutamic oxaloacetic transaminase (GOT) and Aspartate Transaminase (AST) at 1 month, 6 months, 12 months, and 24 months over baseline. | 1, 6, 12, and 24 months over baseline | 
| Glutamic Pyruvic Transaminase (GPT) Alanine Transaminase (ALT) [Full Analysis Data Set] | All data available for glutamic pyruvic transaminase (GPT) Alanine Transaminase (ALT) at 1 month, 6 months, 12 months, and 24 months. | 1, 6, 12, and 24 months over baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tricuspid, Valtech Cardio, Cardioband