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

• ClinicalTrials.gov Identifier: NCT02656290
• Recruitment Status: Completed
• First Posted: January 14, 2016
• Results First Posted: March 17, 2020
• Last Update Posted: February 21, 2023
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Valve Insufficiency; Pulmonary Valve Degeneration; Congenital Pulmonary Valve Abnormality	Device: Edwards Pericardial Aortic Bioprosthesis Model 11000A	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Non-Randomized, Single Arm, Multicenter Clinical Evaluation of the Edwards Pericardial Aortic Bioprosthesis (Model 11000A) for Pulmonary Valve Replacement
• Actual Study Start Date: December 2015
• Actual Primary Completion Date: September 2018
• Actual Study Completion Date: November 28, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percent of Subject's With Freedom From Device or Procedure Related Death and/or Reoperation at 1 Year Post-implant. [ Time Frame: 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.

Secondary Outcome Measures :

1. Percent of Early Adverse Events [ Time Frame: Events occurring within 30 days of procedure ]
   Number of early adverse events occurring within 30 days of procedure divided by the total number of enrolled subjects times 100.
2. Late Adverse Events [ Time Frame: 6 months, and annually for up to 5 years ]
   1) All cause mortality, 2) All/Major paravalvular leak, 3) All/Major transvalvular leak, 4) Endocarditis, 5) Explant, 6) Thromboembolism, 7) Valve-related reoperation, 8) Structural valve deterioration, 9) Non-structural valve deterioration, 10) Trial valve-related mortality, 11) Valve thrombosis, 12) All/Major valve-related bleeding, 13) Hemolysis
3. Subject's Average Mean Gradient [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve.
4. Subject's Average Peak Gradients [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   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.
5. Subject's Amount of Valvular Regurgitation [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   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 and 4 represents severe regurgitation.
6. TR Gradient [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   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.
7. Peak Velocity [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   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.
8. Doppler Velocity Index (DVI) [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   The Doppler Velocity Index (DVI) is a calculation of the ratio of the subvalvular velocity obtained by pulse wave Doppler and the maximum velocity obtained by continuous wave Doppler across the prosthetic valve.
9. Transvalvular VTI [ Time Frame: Baseline, 6 months, and annually thereafter for up to 5 years ]
   Tricuspid valvular regurgitation velocity time interval (VTI) is defined as the measurement in centimeters of the blood flowing backwards through the tricuspid valve, averaged over time.
10. Subject's New York Heart Association (NYHA) Functional Class for Subjects Older Than 12 Years [ Time Frame: Baseline, 30 days, 6 months, and annually thereafter for up to 5 years ]

    The New York Heart Association (NYHA) 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, dyspnea (shortness of breath).

    Class II. Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

    Class III. Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.

    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.

11. Cross-tabulation of New York Heart Association (NYHA) Functional Class for Subjects Older Than 12 Years [ Time Frame: Baseline and 1 Year ]

    The New York Heart Association (NYHA) 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, dyspnea (shortness of breath).

    Class II. Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

    Class III. Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.

    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.

12. Modified Ross Heart Failure Classification for Subjects 12 Years and Under [ Time Frame: Baseline, 30 days, 6 months, and annually for up to 5 years ]

    The Modified Ross Heart Failure classification system relates symptoms to everyday activities and the adolescent patient's quality of life.

    Class I. No limitations or symptoms

    Class II. Infants: Mild tachypnea or diaphoresis with feeding Older children: Mild to moderate dyspnea on exertion

    Class III. Infants: Growth failure and marked tachypnea or diaphoresis with feeding Older children: Marked dyspnea on exertion

    Class IV. Symptoms at rest such as tachypnea, retractions, grunting, or diaphoresis

13. Cross-tabulation of Modified Ross Heart Failure Classification for Subjects 12 Years and Under [ Time Frame: Baseline and 1 Year ]

    The Modified Ross Heart Failure classification system relates symptoms to everyday activities and the adolescent patient's quality of life.

    Class I. No limitations or symptoms

    Class II. Infants: Mild tachypnea or diaphoresis with feeding Older children: Mild to moderate dyspnea on exertion

    Class III. Infants: Growth failure and marked tachypnea or diaphoresis with feeding Older children: Marked dyspnea on exertion

    Class IV. Symptoms at rest such as tachypnea, retractions, grunting, or diaphoresis

Other Outcome Measures:

1. Subject's Average White Blood Cell Count [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]
   Laboratory analysis of White Blood Cell Count on blood drawn from subject; WBC fight infection.
2. Subject's Average Red Blood Cells Count [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]
   Laboratory Analysis of Red Blood Cell Count on blood drawn from subjects; RBC carry oxygen.
3. Subject's Average Hemoglobin Count [ Time Frame: Baseline, 30 days, 6 months, and annually for up to 5 years ]
   Laboratory Analysis of Hemoglobin Count on blood drawn from subjects. Hemoglobin is an oxygen-carrying protein in red blood cells.
4. Subject's Average Hematocrit Percentage [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]
   Laboratory Analysis of Hematocrit Percentage on blood drawn from subjects. Hematocrit is the proportion of red blood cells to the fluid component(plasma) in the blood.
5. Subject's Average Platelet Count [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]
   Laboratory Analysis of Platelet Count on blood drawn from subjects; platelets help with blood clotting.
6. Subject's Average Plasma Free Hemoglobin or Haptoglobin or Serum LDH [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]

   Laboratory Analysis on blood drawn from subjects. Plasma free hemoglobin test measures the level of free hemoglobin in the liquid part of the blood (the serum).

   Haptoglobin is a protein produced by the liver. The lactate dehydrogenase (LDH) test looks for signs of damage to the body's tissues.

7. Subject's Average International Normalized Ratio(INR)/Partial Thromboplastin Time(PTT) [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]

   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.

   PTT is a blood test that looks at how long it takes for the blood to clot.

8. Urine Urobilinogen (if Necessary for Subjects 12 Years and Under) [ Time Frame: Baseline, 6 months, and annually for up to 5 years ]
   Laboratory Analysis of urobilinogen in urine measures the amount of urobilinogen in a urine sample. Urobilinogen is formed from the reduction of bilirubin. Bilirubin is a yellowish substance found in your liver that helps break down red blood cells.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Edwards Lifesciences

Investigators

• Principal Investigator: Christopher Baird, MD; Boston Children's Hospital

  Study Documents (Full-Text)

Documents provided by Edwards Lifesciences:

Study Protocol and Statistical Analysis Plan  [PDF] August 4, 2017

More Information

• Responsible Party: Edwards Lifesciences
• ClinicalTrials.gov Identifier: NCT02656290
• Other Study ID Numbers: 2015-03
• First Posted: January 14, 2016
• Results First Posted: March 17, 2020
• Last Update Posted: February 21, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data will not be available to other researchers

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:

Pulmonary Valve Insufficiency; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases