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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Valve Insufficiency; Pulmonary Valve Degeneration; Congenital Pulmonary Valve Abnormality
• Intervention / Treatment: Device: Edwards Pericardial Aortic Bioprosthesis Model 11000A

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has pulmonary valve disease requiring pulmonary valve replacement of their native or prosthetic valve
2. Is greater than or equal to 5 years of age
3. 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:

1. Valve-in-conduit procedure
2. Requires emergency surgery
3. Has acute myocardial infarction (MI) within 30 days prior to screening date
4. Has MRI or CT scan confirmed stroke, cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months (180 days) prior to screening date
5. Has hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days prior to screening date
6. Has active endocarditis/myocarditis or endocarditis/myocarditis within 3 months prior to screening date
7. 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
8. 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
9. Diagnosed with abnormal calcium metabolism and/or hyperparathyroidism
10. Echocardiographic evidence of an intra-cardiac mass, thrombus, or vegetation
11. RVOT aneurysm unless treated during pulmonary valve replacement surgery
12. Has prior organ transplant or is currently an organ transplant candidate
13. Was previously implanted with INSPIRIS RESILIA Pulmonary valve
14. Previously implanted with an aortic, mitral, or tricuspid bioprosthetic valve, mechanical valve, or annuloplasty ring
15. Need for concomitant replacement of the aortic, mitral or tricuspid valves
16. Has presence of non-cardiac disease limiting life expectancy to less than 12 months
17. Is Currently or has recently participated (within 6 weeks) in another investigational drug or device trial
18. 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
19. Has left ventricular ejection fraction ≤20% as validated by diagnostic procedure prior to screening date
20. Currently incarcerated or unable to give voluntary informed consent
21. Documented history of substance (drug or alcohol) abuse within the last 5 years prior to screening date
22. Patients with hypersensitivity to metal alloys that contain cobalt, chromium, nickel, molybdenum, manganese, carbon, beryllium and iron

23. Patients with hypersensitivity to latex

    Intra-Op Exclusion Criterion:

24. Significant injury to the heart upon entry defined as emergent cardiopulmonary bypass requiring femoral cannulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edwards Pericardial Aortic Bioprosthesis Model 11000A; Pulmonary valve replacement	Device: Edwards Pericardial Aortic Bioprosthesis Model 11000A; Edwards Aortic Bioprosthesis Model 11000A in the pulmonary position; a trileaflet bioprosthesis comprised of bovine pericardium

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject's Average White Blood Cell Count	Laboratory analysis of White Blood Cell (WBC) count on blood drawn from subject; WBC fight infection. The normal reference range for WBC count is 4.5 to 10.0 10^3 cells/microliters. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Red Blood Cell Count	The red blood cell (RBC) count is a test that measures the number of oxygen-carrying blood cells in your blood. The red blood cell count normal range for women is 4.2 to 5.4 10^6 cells/microliters and for men is 4.7 to 6.1 10^6 cells/microliters. A high red blood cell count may indicate that you have a condition that's preventing you from getting enough oxygen. A low RBC may be caused by an infection, or a medical condition related to anemia. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Hemoglobin Count	This is the laboratory analysis of Hemoglobin count on blood drawn from subjects. Hemoglobin is an oxygen-carrying protein in red blood cells. In males, a healthy hemoglobin level is between 13.2 and 16.6 g/dL. In females, a hemoglobin count of between 11.6 and 15 g/dL is considered normal and healthy. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Hematocrit Percentage	This is laboratory analysis of Hematocrit percentage on blood drawn from subjects. A hematocrit test measures the proportion of red blood cells in your blood. Red blood cells carry oxygen throughout your body. Having too few or too many red blood cells can be a sign of certain diseases. Normal hematocrit ranges for adult females are 36% to 44% and for adult males are 41% to 50%. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Platelet Count	This is laboratory analysis of Platelet count on blood drawn from subjects. The purpose of platelets is to create hemostasis, which is the prevention of hemorrhaging (bleeding) and the process of keeping blood inside the vessel walls. A normal platelet range is 150 to 450 10^3 cells/microliter. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Serum LDH	The lactate dehydrogenase (LDH) test looks for signs of damage to the body's tissues. Normal levels of LDH in the blood can vary depending on the lab, but usually range between 140 units per liter (U/L) to 280 U/L for adults and tend to be higher for children and teens.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Plasma Free Hemoglobin	Laboratory Analysis of Plasma Free Hemoglobin (Hgb) of blood drawn from subject. This blood test measures the level of free hemoglobin in the plasma (liquid portion of the blood). The reference range for plasma free hemoglobin is 0.0 to 15.2 mg/dL. In general, values higher than this can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average International Normalized Ratio (INR)	The INR is a calculation based on results of a prothrombin time (PT). The PT is a blood test that measures the time it takes for the liquid portion (plasma) of the blood to clot. The normal range of INR depends on the patient. If they are not on an anticoagulant therapy, then the normal range is 0.9 - 1.1 and if they are on anticoagulant therapy then the normal range is 2 - 3.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years
Subject's Average Urine Urobilinogen (if Necessary for Subjects 12 Years and Under)	Urobilinogen is a substance that is produced when bilirubin, a waste product produced by the breakdown of red blood cells, is processed in the liver and released into the intestine. The normal range of urobilinogen is less than 1 mg/dL. It is common to have values within the 0 to 8 mg/dL range. In general, results either lower or higher than the normal range can indicate something is wrong.	Baseline, Discharge, 30 days, 3 months, and annually for up to 5 years

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Christopher Baird, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (Estimated): January 14, 2016

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Pulmonary Valve Insufficiency
• Other Study ID Numbers: 2015-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be available to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes