Early Feasibility Study of the Cardiac Implants Percutaneous Ring Annuloplasty System

Study Overview
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Brief Summary
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An early feasibility study to evaluate the safety and performance of 1) the transcatheter delivery and implantation of the Cardiac Implants (CI) annuloplasty ring and 2) the adjustment of the ring approximately 90 days following implantation in patients suffering from ≥ moderate functional tricuspid regurgitation (FTR).

Detailed Description
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An early feasibility, multi-center, prospective, single-arm, non-randomized study to assess the safety and performance of the CI Percutaneous Ring Annuloplasty System in patients suffering from ≥ moderate functional tricuspid regurgitation (FTR). Additional outcomes include short and long-term changes in echocardiographic, functional, and quality of life parameters post-adjustment. The CI Ring Annuloplasty System is a percutaneous transcatheter repair device delivered by right heart catheterization through the right internal jugular vein. The System is designed to perform annuloplasty using a Ring Delivery System (RDS) to place a complete, flexible ring over the tricuspid annulus on the atrial side of the valve. Fluoroscopy and transesophageal echocardiography are used to guide and monitor the ring placement procedure. After implantation, the ring becomes embedded within the fibrous tissue of the tricuspid annulus. Approximately 3 months following implantation, the ring is manually adjusted under echocardiographic and fluoroscopic imaging using an Adjustment Tool (AT) until desired reduction of the tricuspid annulus dimension is achieved. Following adjustment, the AT releases a fastener, securing the ring once optimal annular reduction is achieved.

Official Title
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Early Feasibility Study (EFS) of the Cardiac Implants Percutaneous Ring Annuloplasty System for the Treatment of Functional Tricuspid Regurgitation

Conditions
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Tricuspid Regurgitation Functional

Intervention / Treatment
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* Device: CI Percutaneous Ring Annuloplasty System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe functional tricuspid regurgitation (TR) defined by ASE guidelines and the European Association of Echocardiography guidelines. Tricuspid valve annular diameter ≥ 40mm or > 21 mm/m2 as measured by baseline TTE in a 4-chamber view within 90 days prior to index implant procedure. Age ≥ 18 years old at the time of enrollment. New York Heart Associate Classification ≥ II. Symptoms of right heart failure despite optimized medical therapy. Multidisciplinary heart team (minimum of four physicians, including imaging, Structural Heart Disease Interventionalist, Heart Failure Cardiologist, and Cardiac Surgeon) agree that percutaneous tricuspid annuloplasty is a reasonable treatment. Left Ventricular Ejection Fraction (LVEF) ≥ 30% within 90 days prior to index implant procedure The subject has suitable anatomy for investigational device implantation as per imaging requirements. The subject has read and signed the informed consent prior to study related procedures. The subject is willing and able to comply with all required follow-up evaluations and assessments. Exclusion Criteria: Acute decompensated heart failure requiring hospital admission with 4 weeks of enrollment. Severe RV dysfunction as assessed by echocardiography. Primary (organic) tricuspid pathology (e.g. rheumatic, congenital, infective, etc.). Currently participating in another investigational drug or device study. Systolic pulmonary arterial pressure (sPAP) > 70 mmHg as measured by Transthoracic Echocardiography (TTE). Subject requiring another cardiac procedure in the framework of the index procedure; subject requiring a percutaneous procedure within 30 days before or after the procedure or a cardiac surgical procedure within 3 months before or after the procedure. Tricuspid valve stenosis. Aortic, mitral and/or pulmonic valve stenosis and/or regurgitation more than moderate. Intra-cardiac thrombus, mass or vegetation requiring active treatment. Prior tricuspid repair or tricuspid replacement. Known allergy to contrast media, stainless steel or nitinol that cannot be adequately pre-medicated. History of cardiac transplantation. Contraindication to Transthoracic/Transesophageal Echocardiography (TTE/TEE). Endocarditis or severe infection within 12 months of scheduled implant procedure. Myocardial Infarction (MI), percutaneous coronary intervention (PCI), or known unstable angina within the 60 days prior to the index procedure. Cerebro-Vascular Accident within the previous 3 months. Hemodynamic instability or on IV inotropes. Contraindication to anticoagulant therapy and dual antiplatelet therapy. Documented history of bleeding diathesis, hypercoagulable or active peptic ulcer or gastrointestinal bleeding within 3 months of scheduled implant procedure. Severe renal impairment or on dialysis. Any condition that, in the opinion of the investigator, may render the subject unable to complete the study (e.g. life expectancy < 1 year), or lead to difficulties for subject compliance with study requirements. Acute anemia. Chronic Oral Steroid Use ≥ 6 months. Pregnant or lactating female of childbearing potential with a positive pregnancy test 24 hours before any study-related radiation exposure. Pulmonary embolism within the last 6 months. Tricuspid Valve Tethering distance > 10 mm. Presence of transvalvular pacemaker or defibrillator leads which are determined as immobile or interfering with the procedure, as evaluated by echocardiography. Inadequate TEE acoustic window for appropriate visualization of the tricuspid valve that is required for guiding the index implant procedure. Contra-indicated for blood transfusion or refuses transfusion. Patient undergoing emergency treatment. Patient without appropriate jugular access.

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 |
| --- | --- |
| Experimental: CI Percutaneous Ring Annuloplasty System<br>Patients treated with the CI Percutaneous Ring Annuloplasty System | Device: CI Percutaneous Ring Annuloplasty System<br>* Percutaneous transcatheter implant and adjustment of the CI ring annuloplasty system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from device or procedure-related mortality | Freedom from mortality determined to be primarily caused by the device or procedure in the primary endpoint cohort. Events adjudicated by a Clinical Events Committee (CEC). | 30 days post-adjustment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of device or procedure-related major adverse events (MAE) | The incidence of MAEs determined to be primarily caused by the device or procedure. Events adjudicated by CEC. | 30, 60, and 90 days post-implant; 30 days, 3 months, 6 months, 12 months, and 2-5 years (annually) post-adjustment | 
| Technical: Proportion of successful access, delivery, and retrieval device delivery system | The proportion of successful access, delivery, and retrieval of the device delivery system. | 30 days post-implant and 30 days post-adjustment | 
| Technical: Proportion of successful deployment and positioning of the ring implant. | The proportion of successful deployment and correct/stable positioning of the ring implant. | 30 days post-implant and 30 days post-adjustment | 
| Technical: Freedom from emergency surgery or reintervention | The proportion of subjects free from emergency surgery or reintervention casually related to the device or access procedure. | 30 days post-implant and 30 days post-adjustment | 
| Technical: Rate of Successful Implants | The proportion of subjects with successful ring implants. | 30 days post-implant | 
| Technical: Proportion of Successful Procedures | Proportion of successful procedures, as defined in Mitral Valve Academic Research Consortium (MVARC) | 30 days post-implant and 30 days post-adjustment | 
| Technical: Number of device stakes embedded in tissue | Proportion of device stakes embedded in tissue vs. stakes remain embedded at follow-up, per subject, as assessed through multi-modality imaging (i.e. fluoroscopy, cine, TEE, and Cardiac CT) and evaluated by an independent Core Lab(s). | 30 days post-implant, 30 days post-adjustment, and 1 year post-adjustment | 
| Mechanistic: Changes in TR Severity | The changes in TR severity, characterized per the American Society of Echocardiography (ASE) guidelines, as compared to baseline, to be evaluated by independent Core Lab. | 30 and 90 days post-implant; and 30, 90, 180, and 1-2 years (annually) post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes Tricuspid Valve (TV) Annular Diameter | Changes in TV annular diameter as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in TV Area | Changes in TV area as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Vena Contracta (VC) dimensions | Changes in VC dimensions as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Proximal isovelocity surface area (PISA) effective regurgitant orifice area (EROA) | Changes in PISA EROA as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Quantitive EROA | Changes in quantitative EROA as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in TV Regurgitant Volume | Changes in TV regurgitant volume as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Right Atrium (RA) Dimensions | Changes in RA dimensions as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Right Ventricle (RV) Dimensions | Changes in RV dimensions (cm) as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Inferior Vena Cava (IVC) Dimensions | Changes in IVC dimensions as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) | Changes in TAPSE as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Left Atrium (LA) Dimensions | Changes in LA dimensions as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Mechanistic: Echocardiographic changes: Changes in Left Ventricle (LV) Dimensions | Changes in LV dimensions as compared to baseline, determined via echocardiography. | 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment | 
| Functional: Changes in NYHA Classification | Changes in New York Heart Association (NYHA) classification as compared to baseline. | 1 year post-adjustment | 
| Functional: Changes in Distance Walked for Exercise Tolerance | Changes in distance walked, assessed by 6 Minute Walk Test | 1 year post-adjustment | 
| Functional: Changes in Quality of Life Scores and Sub-Domains | Changes in quality of life overall score and sub-domains in comparison to baseline values as evaluated by the Kansas City Cardiomyopathy Questionnaire (KCCQ) | 1 year post-adjustment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tricuspid Valve, Annular Dilatation, Annuloplasty, Tricuspid Valve Repair