COMMENCE Pulmonary: Clinical Evaluation of Edwards Pericardial Aortic Bioprosthesis (Model 11000A) for Pulmonary Valve Replacement

Study Overview
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Brief Summary
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The objective of this trial is to assess the safety and effectiveness of the Edwards Pericardial Aortic Bioprosthesis Model 11000A, in the pulmonary position in pediatric and adult subjects five years or older requiring replacement of their native or prosthetic pulmonary valve.

Detailed Description
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This is a prospective, Non-Randomized, Single Arm, Multicenter study. Up to one hundred (100) pulmonary valve replacement (PVR) subjects at up to ten (10) clinical sites will be enrolled. Clinical data will be collected from at least 3 centers with data available on patients who have completed the 1 year follow-up visit. Subjects will be followed for and assessed after implant for up to 5 years.

Official Title
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Prospective, Non-Randomized, Single Arm, Multicenter Clinical Evaluation of the Edwards Pericardial Aortic Bioprosthesis (Model 11000A) for Pulmonary Valve Replacement

Conditions
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Pulmonary Valve Insufficiency, Pulmonary Valve Degeneration, Congenital Pulmonary Valve Abnormality

Intervention / Treatment
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* Device: Edwards Pericardial Aortic Bioprosthesis Model 11000A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has pulmonary valve disease requiring pulmonary valve replacement of their native or prosthetic valve Is greater than or equal to 5 years of age Subject and/or subject's legal representative has provided written informed consent as approved and required by the respective institutional review board and agrees to its provisions. NOTE: Written consent must be obtained prior to any research related test being performed. Exclusion criteria: A subject meeting any of the following criteria shall be excluded: Valve-in-conduit procedure Requires emergency surgery Has acute myocardial infarction (MI) within 30 days prior to screening date Has MRI or CT scan confirmed stroke, cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months (180 days) prior to screening date Has hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days prior to screening date Has active endocarditis/myocarditis or endocarditis/myocarditis within 3 months prior to screening date Has renal insufficiency as determined by creatinine (S-Cr) level   2.5 mg/dL within 60 days prior to screening visit or end-stage renal disease Has documented leukopenia (WBC < 3.5x 103/I-lL), acute anemia (Hgb <10.0 g/dL or 6 mmol/L), or thrombocytopenia (platelet count < 50xl03/I-lL) accompanied by history of bleeding diathesis or coagulopathy within 60 days prior to screening date Diagnosed with abnormal calcium metabolism and/or hyperparathyroidism Echocardiographic evidence of an intra-cardiac mass, thrombus, or vegetation RVOT aneurysm unless treated during pulmonary valve replacement surgery Has prior organ transplant or is currently an organ transplant candidate Was previously implanted with INSPIRIS RESILIA Pulmonary valve Previously implanted with an aortic, mitral, or tricuspid bioprosthetic valve, mechanical valve, or annuloplasty ring Need for concomitant replacement of the aortic, mitral or tricuspid valves Has presence of non-cardiac disease limiting life expectancy to less than 12 months Is Currently or has recently participated (within 6 weeks) in another investigational drug or device trial Positive urine or serum pregnancy test in female subjects of child-bearing potential and/or nursing mothers, or planning to become pregnant within 1 year of study valve implant Has left ventricular ejection fraction ≤20% as validated by diagnostic procedure prior to screening date Currently incarcerated or unable to give voluntary informed consent Documented history of substance (drug or alcohol) abuse within the last 5 years prior to screening date Patients with hypersensitivity to metal alloys that contain cobalt, chromium, nickel, molybdenum, manganese, carbon, beryllium and iron Patients with hypersensitivity to latex Intra-Op Exclusion Criterion: Significant injury to the heart upon entry defined as emergent cardiopulmonary bypass requiring femoral cannulation

Ages Eligible for Study
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Minimum Age: 5 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: Edwards Pericardial Aortic Bioprosthesis Model 11000A<br>Pulmonary valve replacement | Device: Edwards Pericardial Aortic Bioprosthesis Model 11000A<br>* Edwards Aortic Bioprosthesis Model 11000A in the pulmonary position; a trileaflet bioprosthesis comprised of bovine pericardium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subject's With Freedom From Device or Procedure Related Death and/or Reoperation at 1-year Post-implant. | Subject's freedom from device or procedure related death and/or reoperation at 1-year post-implant. Time to events were estimated by Kaplan-Meier method. A higher number means a better outcome. | 1-year post-implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Early Adverse Events | Number of early adverse events occurring within 30 days of procedure divided by the total number of enrolled subjects times 100. | Percentage of events occurring within 30 days of procedure | 
| Number of Late Adverse Events Divided by Late Patient Years (Expressed as a Percentage) for the Trial Valve Cohort. | Late patient years are calculated from 31 days post-implant to the date of the last follow-up visit (or contact) or adverse event. Late patient year calculation: [(Number of late events/sum of late patient years) x 100] | Events occurring ≥ 31 days and up through 5 years post implant. | 
| Subject's Average Mean Gradient Measurements Over Time. | Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. In general, a higher value is considered worse, and a lower value is considered better but the value is dependent on the size and type of valve. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Subject's Average Peak Gradient Measurements Over Time. | Peak gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. In general, a higher value is considered worse, and a lower value is considered better but the value is dependent on the size and type of valve. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Amount of Paravalvular Pulmonary Regurgitation in Subjects Over Time by Valve Size | Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing. Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation/leak (a better outcome) and 4 represents severe regurgitation/leak (a worse outcome). | Discharge, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Amount of Transvalvular Pulmonary Regurgitation in Subjects Over Time by Valve Size | Valvular regurgitation occurs when the valve in the heart does not close tightly allowing some of the blood that was pumped out of the heart to leak back into it. Valvular regurgitation is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation (a better outcome) and 4 represents severe regurgitation (a worse outcome). | Discharge, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Subject's Average Tricuspid Regurgitation (TR) Gradient Measurement Over Time. | Tricuspid regurgitation (TR) gradient (peak systolic) is defined as the maximum value measured of blood flowing back through the tricuspid valve during systole as measured in millimeters of mercury. In general, a higher value is considered worse, and a lower value is considered better but the value is dependent on the size and type of valve. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Subject's Average Peak Velocity Measurement Over Time | Peak velocity is defined as the maximum speed in meters per second that the blood is flowing through the pulmonic heart valve in a given direction. In general, a higher value is considered worse, and a lower value is considered better but the value is dependent on the size and type of valve. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Subject's Average Doppler Velocity Index (DVI) | The Doppler Velocity Index (DVI) is a calculation of the ratio of the sub valvular velocity obtained by pulse wave Doppler and the maximum velocity obtained by continuous wave Doppler across the prosthetic valve, i.e. Time velocity interval (TVI) of the pulmonic valve / TVI of the RVOT. There are no normal ranges issued by the American Society of Echocardiography's Guidelines and Standards Committee for the pulmonary valve, however the expectation is that DVI should remain relatively steady over time but will generally decrease as the degree of stenosis (narrowing or constriction of the valve opening) worsens. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Subject's Average Transvalvular Velocity Time Interval (VTI) | Transvalvular regurgitation velocity time interval (VTI) is defined as the measurement in centimeters of the blood flowing backwards through the tricuspid valve, averaged over time. There are no defined normal ranges for VTI. The VTI value is dependent on the function of the right ventricle of the heart (chamber within the heart that is responsible for pumping oxygen-depleted blood to the lungs) and the expectation is the value should be relatively steady over time. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years | 
| Change in Subject's New York Heart Association (NYHA)/Modified Ross Heart Failure Functional Class | The New York Heart Association (NYHA)/Modified Ross functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, shortness of breath. Class II. Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath. Class III. Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or shortness of breath. Class IV. Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. Changes in NYHA/Modified Ross HF classification from the preoperative baseline to the respective completed follow-up visits are shown as the number of subjects in each class who improved, worsened, or stayed the same. | Baseline, 30 days, 3 months, and annually thereafter for up to 5 years |