Edwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial

Study Overview
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Brief Summary
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To establish the safety and effectiveness of the Edwards PASCAL Transcatheter Repair System in patients with symptomatic severe tricuspid regurgitation who have been determined to be at an intermediate or greater estimated risk of mortality with tricuspid valve surgery by the cardiac surgeon with concurrence by the local Heart Team

Detailed Description
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A Prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter tricuspid valve repair with the Edwards PASCAL Transcatheter Valve Repair System and optimal medical therapy (OMT) compared to OMT alone in patients with tricuspid regurgitation. Patients will be seen for follow-up visits at discharge, 30 days, 3 months, 6 months, and annually through 5 years.

Official Title
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A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Tricuspid Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System and Optimal Medical Therapy (OMT) Compared to OMT Alone in Patients With Tricuspid Regurgitation

Conditions
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Tricuspid Regurgitation, Tricuspid Valve Insufficiency, Tricuspid Valve Disease

Intervention / Treatment
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* Device: Edwards PASCAL System
* Drug: Optimal Medical Therapy
* Device: Edwards PASCAL System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen (18) years of age or older Despite medical therapy, per the local Heart Team, patient has signs of TR, symptoms from TR, or prior heart failure hospitalization from TR. Severe or greater tricuspid regurgitation New York Heart Association (NYHA) Class II-IVa or heart failure hospitalization in the prior 12 months Patient is at an intermediate or greater estimated risk of mortality with tricuspid valve surgery as determined by the cardiac surgeon with concurrence by the local Heart Team Patient is able and willing to give informed consent, follow protocol procedures, and comply with follow-up visit requirements Exclusion Criteria: Tricuspid valve anatomy not evaluable by TTE or TEE Tricuspid valve anatomy precludes proper device deployment and function Patient with refractory heart failure requiring, advanced intervention (i.e. patient has or will need left ventricular assist device, or transplantation) (ACC/AHA Stage D heart failure) Presence of trans-tricuspid pacemaker or defibrillator leads which meet one of the following: Would prevent proper TR reduction due to interaction of the lead with the leaflets Were implanted in the RV within the last 90 days prior to the point of enrollment Primary non-degenerative tricuspid disease Previous tricuspid valve repair or replacement that would interfere with placement of PASCAL Clinically significant, untreated coronary artery disease requiring revascularization, unstable angina, evidence of acute coronary syndrome, recent myocardial infarction Significant intra-cardiac mass, thrombus, or vegetation per echo core lab assessment Deep vein thrombosis (DVT) or pulmonary embolism (PE) in the last 90 days Recent Stroke Active gastrointestinal (GI) bleeding Presence of infiltrative cardiomyopathy or valvulopathy (including carcinoid, amyloidosis, sarcoidosis, hemochromatosis) or significant congenital heart disease, including but not limited to atrial septal defect, RV dysplasia, and arrhythmogenic RV Need for emergent or urgent surgery for any reason, any planned cardiac surgery within the next 12 months (365 days), or any planned percutaneous cardiac procedure within the next 90 days Any of the following cardiovascular procedures: Percutaneous coronary, intracardiac, or endovascular intervention within the last 30 days prior to the point of enrollment Carotid surgery within 30 days prior to the point of enrollment Direct current cardioversion within the last 30 days prior to the point of enrollment Leadless RV pacemaker implant within the last 30 days prior to the point of enrollment Cardiac surgery within 90 days prior to the point of enrollment Severe aortic, mitral and/or pulmonic valve stenosis and/or regurgitation Known history of untreated severe symptomatic carotid stenosis or asymptomatic carotid stenosis Active endocarditis within the last 90 days or infection requiring antibiotic therapy within the last 14 days Patient is oxygen-dependent or requires continuous home oxygen Pregnant, breastfeeding, or planning pregnancy within the next 12 months (365 days) Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator Patient is currently participating in another investigational biologic, drug, or device clinical study Patient has other medical, social, or psychological conditions that preclude appropriate consent and follow-up, or the patient is under guardianship Any patient considered to be vulnerable

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edwards PASCAL System & OMT<br>Transcatheter tricuspid valve repair with the Edwards PASCAL system in patients on optimal medical therapy (OMT) with tricuspid regurgitation | Device: Edwards PASCAL System<br>* Transcatheter tricuspid valve repair with the Edwards PASCAL System in patients on optimal medical therapy<br>* Other names: Transcatheter tricuspid valve repair (TTVr);|
| Active Comparator: Optimal Medical Therapy (OMT)<br>Optimal medical therapy (OMT) alone in patients with tricuspid regurgitation | Drug: Optimal Medical Therapy<br>* Optimal Medical Therapy alone in patients with tricuspid regurgitation<br>|
| Experimental: Single-Arm Registry<br>Transcatheter tricuspid valve repair with the Edwards PASCAL System in conjunction with optimal medical therapy (OMT) in patients with tricuspid regurgitation who are not eligible for randomization | Device: Edwards PASCAL System<br>* Transcatheter tricuspid valve repair with the Edwards PASCAL System in conjunction with OMT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint including all-cause mortality, RVAD implantation or heart transplant, tricuspid valve intervention, heart failure hospitalizations, and Quality of Life improvement (measured by KCCQ score) | Comparison of number of participants with composite endpoint events between experimental and active comparator arms | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 Grade Reduction in TR Severity | Total number of participants with at least 1 grade reduction in TR severity | 12 months | 
| Quality of Life (QOL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) | Change in KCCQ score from baseline | 12 months | 
| All Cause Mortality | Total number of deaths from any cause | 12 months, 24 months | 
| Death and Heart Failure Hospitalizations | Total number of deaths and hospital admissions due to heart failure | 12 months | 
| All-cause Hospitalization | Total number of hospitalizations due to any cause | 12 months | 
| Right ventricular end-diastolic diameter (RVEDD mid) | Change in right ventricular end-diastolic diameter (RVEDD mid) | 12 months | 
| Major Adverse Events (MAEs) | Overall rate of Major Adverse Events (MAEs) | 30 days | 
| Reduction in TR grade | Reduction in TR severity as assessed by TEE pre- and post-implantation | Intraprocedural post-implantation | 
| All-Cause Mortality | Total number of deaths from any cause | 12 months, annually through 5 years | 
| Heart failure hospitalizations | Total number of hospital admissions due to heart failure | 12 months, annually through 5 years | 
| Non-elective tricuspid valve re-intervenitions (percutaneous or surgical) | Total number of non-elective tricuspid valve re-interventions | 12 months, annually through 5 years | 
| Durable RVAD implantation or heart transplant | Total number of patients requiring RVAD impantantion or heart transplant | 12 months, annually through 5 years | 
| Need for paracentesis | Total nunber of patients who required paracentesis | 12 months, annually through 5 years |