PARADIGM: Amplatzer Valvular Plug for PVL Closure

Study Overview
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Brief Summary
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The Paradigm study is a prospective, multicenter, single arm study to demonstrate the safety and effectiveness of the AVP III as a treatment for clinically significant PVLs following surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral position.

Detailed Description
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PARADIGM is a prospective, international, multi-center, single arm study to demonstrate the safety and effectiveness of the AVP III for percutaneous, transcatheter closure of PVLs occurring after aortic or mitral valve replacement with a surgically-implanted mechanical or bioprosthetic valve. The study will be conducted at up to 25 clinical sites in the US, EU and Canada, where a total of 200 subjects with a clinically significant PVL will undergo an AVP III implant procedure for PVL closure. Pre-procedural Baseline and follow-up assessments at Discharge, 30 days, 6 months and 1 year will include echocardiography, physical examinations, lab measurements and questionnaires to assess PVL severity, prosthetic valve function, hemolytic anemia, heart failure symptoms, and quality of life. Adverse events will be recorded throughout the study.

Official Title
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PARADIGM PARAvalvular Leak Closure With the Amplatzer Valvular Plug occluDer for Interventional Transcatheter Closure for PVL With Surgical bioloGical and Mechanical Heart Valve

Conditions
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Paravalvular Aortic Regurgitation

Intervention / Treatment
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* Device: Amplatzer Valvular Plug III


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is implanted with a mechanical or biological surgical valve in the aortic or mitral position Note: Subjects in European countries can only be implanted with a mechanical valve in the aortic or mitral position Subject has a clinically significant paravalvular leak with a severity grade of moderate or higher, associated with signs of heart failure and/or hemolysis necessitating recurring blood transfusions. Subject has one clinically significant PVL defect that can be closed with a single AVP III as assessed pre-procedurally Subject has provided written informed consent Subject is ≥18 years old Exclusion Criteria: Subject has a rocking valve or extreme dehiscence of the prosthetic valve involving more than 40% of the sewing ring Subject's PVL(s) originates from a transcatheter aortic or mitral valve replacement, or from rapid deployment or sutureless surgical replacement valves Subject has a prosthetic aortic valve and prosthetic mitral valve which both have a clinically significant paravalvular leak. Subject who is hemodynamically unstable or who cannot undergo an elective procedure Subject with active endocarditis or other active infection Subject has within the last 6 months a previously documented intracardiac mass, vegetation, tumor, or thrombus which would interfere with placement of the AVP III Subject has inadequate vasculature for delivery of the AVP III Subject has unsuitable anatomy for PVL closure using the AVP III (such as a PVL associated with an abscess cavity or a pseudoaneurysmal sac) or anatomy where the AVP III would interfere with other intracardiac or intravascular structures (such coronary ostia) Subjects who are unable to receive intraprocedural anticoagulant therapy Pregnant or nursing subjects or subjects who plan pregnancy during the clinical investigation follow-up period. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results. Life expectancy is less than 1 year in the opinion of the Investigator Incapacitated individuals, defined as persons with mental illnesses or handicaps that impair their ability to provide informed consent, or individuals without legal authority to provide informed consent. Individual who are currently participating in an investigational drug or device study that has not reached the primary endpoint or that may confound the results of this study

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: Paravalvular Leak Closure<br>Includes all eligible subjects who undergo an AVP III implant attempt for treatment of significant paravalvular leakage with an echocardiographic severity grade of moderate or higher. This is a single arm study. | Device: Amplatzer Valvular Plug III<br>* Transcatheter closure of a paravalvular leak using Amplatzer Valvular Plug III<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paravalvular leak closure success rate (percent of subjects) | Defined as AVPIII placement in the intended location without interference with the prosthetic valve or intraprocedural mortality with at least a 2 severity-grade reduction in paravalvular regurgitation at exit from the procedure and freedom from unplanned AVPIII-related transcatheter or surgical reintervention through 30 days post-implant. | 30 Days |