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

Pulmonary Valve Insufficiency Clinical Trial

— COMMENCE-P  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02656290
• Other study ID #: 2015-03
• Status: Completed
• Phase: N/A
• Start date: December 2015
• Est. completion date: November 28, 2022

Study information

• Verified date: November 2023
• Source: Edwards Lifesciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 28, 2022
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Congenital Pulmonary Valve Abnormality
• Pulmonary Valve Degeneration
• Pulmonary Valve Insufficiency

Intervention

Device:
• Edwards Pericardial Aortic Bioprosthesis Model 11000A
Edwards Aortic Bioprosthesis Model 11000A in the pulmonary position; a trileaflet bioprosthesis comprised of bovine pericardium

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Edwards Lifesciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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