ProspeCtive, nOn-randoMized, MulticENter Clinical Evaluation of Edwards Pericardial Bioprostheses With a New Tissue Treatment Platform (COMMENCE) (COMMENCE)

• ClinicalTrials.gov Identifier: NCT01757665
• Recruitment Status: Active, not recruiting
• First Posted: December 31, 2012
• Results First Posted: December 27, 2019
• Last Update Posted: January 25, 2021
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Study Description

Brief Summary:

The objective of this trial is to confirm that the modifications to tissue processing, valve sterilization and packaging do not raise any new questions of safety and effectiveness in subjects who require replacement of their native or prosthetic aortic or mitral valve.

Condition or disease	Intervention/treatment	Phase
Aortic Stenosis; Mitral Stenosis; Aortic Valve Insufficiency; Mitral Valve Insufficiency; Heart Failure	Device: Edwards Aortic and Mitral Bioprostheses Models 11000A and 11000M	Not Applicable

Detailed Description:

Multicenter, prospective, single arm trial - Up to seven hundred (700) aortic valve replacement (AVR) subjects and up to one hundred seventy-five (175) mitral valve replacement (MVR) subjects at up to forty (40) clinical sites will be enrolled. The trial will include male and female patients, 18 years or older, requiring replacement for a diseased, damaged, or malfunctioning native or prosthetic aortic or mitral valve. Patients will be followed and assessed after implant for up to 5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 777 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ProspeCtive, nOn-randoMized, MulticENter Clinical Evaluation of Edwards Pericardial Aortic and Mitral Bioprostheses (Models 11000A and 11000M) With a New Tissue Treatment Platform (COMMENCE)
• Study Start Date: December 2012
• Actual Primary Completion Date: August 2017
• Estimated Study Completion Date: August 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bioprosthesis: Aortic Model 11000A/ Mitral Model 11000M; Aortic/Mitral valve replacement therapy	Device: Edwards Aortic and Mitral Bioprostheses Models 11000A and 11000M; Implant of an aortic valve, Model 11000A or mitral valve, Model 11000M

Outcome Measures

Primary Outcome Measures :

1. Subjects With Structural Valve Deterioration [ Time Frame: 1 Year Post Implant ]
   The rate of implanted subjects that experience structural valve deterioration (SVD) of the trial valve by the time of the post operative day (POD) 390 follow-up visit. Structural valve deterioration includes dysfunction or deterioration intrinsic to the valve. Examples of SVD includes complications such as wear, fracture, calcification, leaflet tear.

Secondary Outcome Measures :

1. Percentage of Subjects With Early Adverse Events [ Time Frame: Events occuring within 30 days of procedure ]
   Number of subjects with early adverse events occurring within 30 days of procedure divided by the number of enrolled subjects times 100
2. Percentage of Late Adverse Events Divided by Late Patient Years [ Time Frame: Events occurring >= 31 days and up through 3 years post-implant ]
   Number of late events divided by the total number of late patient years times 100. Late patient years are calculated from 31 days post-implant to the date of the last contact (follow up or adverse event).

Other Outcome Measures:

1. Subject's Average Mean Gradient Measurements - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Year Post Implant ]
   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.
2. Subject's Average Mean Gradient Measurements - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Mean gradient is the average flow of blood through the mitral valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve.
3. Subject's Average Peak Gradients Measurements Over Time - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   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.
4. Subject's Average Peak Gradients Measurements Over Time - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Peak gradient is the maximum value measured of flow of blood through the mitral valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time.
5. Subject's Average Effective Orifice Area Measurements - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Effective orifice area represents the cross-sectional area of the blood flow downstream of the aortic valve. Effective orifice area is evaluated by echocardiography over time.
6. Subject's Average Effective Orifice Area Measurements - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Effective orifice area represents the cross-sectional area of the blood flow downstream of the mitral valve. Effective orifice area is evaluated by echocardiography over time.
7. Subject's Average Effective Orifice Area Index (EOAI) Measurements - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the aortic valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time.
8. Subject's Average Effective Orifice Area Index (EOAI) Measurements - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the mitral valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time.
9. Subject's Average Performance Index Measurements - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
   Performance index is defined as the subject's effective orifice area (the cross sectional area of the blood flow downstream of the aortic valve) divided by the subject's native orifice area. Effective orifice area is evaluated by echocardiography over time.
10. Subject's Average Performance Index Measurements - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    Performance index is defined as the subject's effective orifice area (the crosssectional area of the blood flow downstream of the mitral valve) divided by the subject's native orifice area. Effective orifice area is evaluated by echocardiography over time.
11. Subject's Average Cardiac Output Over Time - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    The amount of blood the heart pumps through the circulatory system in a minute.
12. Subject's Average Cardiac Output Over Time - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    The amount of blood the heart pumps through the circulatory system in a minute.
13. Subject's Average Cardiac Index Over Time- 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    Cardiac index is an assessment that divides the cardiac output from left ventricle in one minute by the person's body surface area (BSA), thus relating heart performance to the size of the individual.
14. Subject's Average Cardiac Index Over Time - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    Cardiac index is an assessment that divides the cardiac output from left ventricle in one minute by the person's body surface area(BSA), thus relating heart performance to the size of the individual.
15. Subject's Amount of Total Valvular Regurgitation Over Time - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    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.
16. Subject's Amount of Total Valvular Regurgitation Over Time - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]
    Mitral valvular regurgitation occurs when the mitral 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. Mitral 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.
17. Subject's Amount of Paravalvular Leak Over Time - 11000A [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]

    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 minimum of 0 to maximum of 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. Higher numbers on the scale show a worsening outcome.

18. Subject's Amount of Paravalvular Leak Over Time - 11000M [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]

    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 minimum of 0 to maximum of 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. Higher numbers on the scale show a worsening outcome.

19. Subject's New York Heart Association (NYHA) Functional Class Compared to Baseline [ Time Frame: 3 Months, 1 Year, and 2 Years Post Implant ]

    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.

20. Subject's Average Score at Baseline and 1 Year on the Quality of Life Survey [ Time Frame: Baseline and one year post-implant ]

    The Medical Outcomes Study Short-Form 12 (SF-12) contains two components - the Physical Component Summary (PCS) and the Mental Component Summary (MCS).

    The SF-12 Physical Component Summary questionnaire scale ranges from a maximum of 100, which reflects the best health status to a minimum of 0, which reflects the worst health status.

    The SF-12 Mental Component Summary scale ranges from a maximum of 100, which reflects the best health status to a minimum of 0, which reflects the worst health status.

21. Subject's Average White Blood Cell Count [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory analysis of White Blood Cell (WBC) count on blood drawn from subject; WBC fight infection.
22. Subject's Average Red Blood Cells Count [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of Red Blood Cell (RBC) Count on blood drawn from subjects; RBC carry oxygen.
23. Subject's Average Hematocrit Percentage [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of Hematocrit Percentage on blood drawn from subjects. Hematocrit is the proportion of red blood cells to the plasma (liquid portion of the blood).
24. Subject's Average Hemoglobin Count [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of Hemoglobin Count on blood drawn from subjects. Hemoglobin is an oxygen-carrying protein in red blood cells.
25. Subject's Average Platelet Count [ Time Frame: Baseline, Discharge, 3 Months, 1 Year, and 2 Years ]
    Laboratory Analysis of Platelet Count on blood drawn from subjects; platelets help with blood clotting.
26. Subject's Average Plasma Free Hemoglobin [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of Plasma Free Hemoglobin on blood drawn from subjects. This blood test measures the level of free hemoglobin in the plasma (liquid portion of the blood).
27. Subject's Average International Normalized Ratio [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of International Normalized Ratio (INR) on blood drawn from subjects. 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 plasma (liquid portion of the blood) to clot. INR results will vary according to a person's age, the medicines they take, and any health problems they may have. In general, the higher the INR number, the longer it takes for the blood to clot. In healthy people an INR of 1.1 or below is considered normal. An INR range of 2.0 to 3.0 is generally an effective therapeutic range for people taking blood thinner medication.
28. Subject's Average Partial Thromboplastin Time [ Time Frame: Baseline, Discharge, 3 Months, 1 Year and 2 Year ]
    Laboratory Analysis of partial thromboplastin time (PTT) on blood drawn from subjects. PTT is a blood test that looks at how long it takes for the blood to clot.
29. Subject's Average Prothrombin Time [ Time Frame: Baseline, Discharge, 3 Months, 1 Year, and 2 Years ]
    Laboratory Analysis of Prothrombin Time (PT) on blood drawn from subjects. The PT is a blood test that measures the time it takes for the plasma (liquid portion of the blood) to clot.
30. Subjects Average Serum Glycerol Levels [ Time Frame: Pre-Implant (post-heparinization) and Post-Implant (between 60 and 120 minutes after heart was restarted) ]
    Laboratory analysis of serum glycerol in blood drawn from subjects. This blood test measures the amount of glycerol (a naturally occurring carbohydrate, that can be used as a fuel source by the body) in the serum (liquid portion of the blood).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Eligibility Criteria:

Inclusion Criteria:

1. Is 18 years or older
2. Provides written informed consent prior to trial procedures
3. Agrees to attend all follow-up assessments for up to 5 years and is willing to comply with specified follow-up evaluations at clinical investigational sites that are participating in the COMMENCE trial and/or obtain the protocol-specified diagnostic tests at centers that are under the same IRB or the same healthcare system
4. Diagnosed with aortic or mitral valve disease requiring valve replacement based on pre- operative evaluation
5. Scheduled to undergo planned aortic or mitral valve replacement with or without concomitant bypass surgery
6. Scheduled to undergo planned aortic valve replacement with or without resection and replacement of the ascending aorta from the sinotubular junction and without the need for circulatory arrest for hemi arch or arch replacement

Exclusion criteria:

A subject meeting any of the following criteria shall be excluded:

1. Requires emergency surgery
2. Requires planned multiple valve replacement/ repair (with the exception of mitral valve replacement with tricuspid valve repair)
3. Has prior valve surgery, which included implant of a bioprosthetic valve, mechanical valve, or annuloplasty ring that will remain in situ
4. Requires a surgical procedure outside of the cardiac area (e.g. vascular bypass)
5. Requires surgical replacement of the aortic root
6. Has active endocarditis/myocarditis or endocarditis/myocarditis within 3 months to the scheduled aortic or mitral valve replacement surgery
7. Has renal insufficiency as determined by creatinine (S-Cr) level ≥ 2.5 mg/dL or end -stage renal disease requiring chronic dialysis at screening visit
8. Has MRI or CT scan confirmed stroke, cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months (180 days) prior to planned valve surgery
9. Has acute myocardial infarction (MI) within 30 days prior to planned valve surgery
10. Has presence of non-cardiac disease limiting life expectancy to less than 12 months
11. Diagnosed with hypertrophic obstructive cardiomyopathy (HOCM)
12. Diagnosed with abnormal calcium metabolism and hyperparathyroidism
13. Exhibits left ventricular ejection fraction ≤ 20% as validated by diagnostic procedure prior to planned valve surgery
14. Echocardiographic evidence of an intra-cardiac mass, thrombus, or vegetation
15. Hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days prior to planned valve surgery
16. Documented leukopenia (WBC < 3.5x 10³/μL), acute anemia (Hgb < 10.0 gm/dL or 6 mmol/L) or thrombocytopenia (platelet count < 50x 10³/μL) accompanied by history of bleeding diathesis and coagulopathy
17. Has prior organ transplant or is currently an organ transplant candidate
18. Current or recent participation (within 6 weeks prior to surgery) in another drug or device trial
19. Was previously implanted with trial device (Model 11000A or Model 11000M)
20. Pregnant (female subject of childbearing potential only), lactating or planning to become pregnant during the duration of participation in trial
21. Currently incarcerated or unable to give voluntary informed consent
22. Documented history of substance (drug or alcohol) abuse within the last 5 years prior to implant
23. Requires concomitant left ventricular assist device (LVAD) placement

Contacts and Locations

Locations

United States, Alabama

Cardiology, P.C.

Birmingham, Alabama, United States, 35211

United States, California

University of Southern California

Los Angeles, California, United States, 90033

Sutter Institute for Medical Research

Sacramento, California, United States, 95919

Board of Trustees of the Leland Stanford Junior University

Stanford, California, United States, 94305

United States, Connecticut

Yale-New Haven

New Haven, Connecticut, United States, 06519

United States, Florida

Shands at the University of Florida

Gainesville, Florida, United States, 32610

Florida Hospital

Orlando, Florida, United States, 32803

United States, Georgia

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

United States, Indiana

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, United States, 46290

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Maryland

University of Maryland, Baltimore

Baltimore, Maryland, United States, 21201

United States, Michigan

Spectrum Health Hospital

Grand Rapids, Michigan, United States, 49503

United States, Mississippi

North Mississippi Medical Center

Tupelo, Mississippi, United States, 38801

United States, Missouri

Missouri Baptist Medical Center

Saint Louis, Missouri, United States, 36131

Washington University/ Barnes Jewish Hospital

Saint Louis, Missouri, United States, 63110

United States, New York

Mount Sinai Beth Israel

New York, New York, United States, 10003

New York Weill Cornell Medical Center

New York, New York, United States, 10021

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States, 10032

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

OhioHealth Research Institute

Columbus, Ohio, United States, 43124

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Pinnacle Health Cardiovascular Institute

Harrisburg, Pennsylvania, United States, 17403

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19016

United States, Tennessee

St. Thomas Health

Nashville, Tennessee, United States, 37205

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Michael E. DeBakey VA Medical Center

Houston, Texas, United States, 77030

The Heart Hospital of Baylor Plano

Plano, Texas, United States, 75093

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Quebec, Canada, G1V 4G5

Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, Poland, 31-202

The Cardinal Stefan Wyszynski Institute of Cardiology

Warsaw, Poland, 04-628

Sponsors and Collaborators

Edwards Lifesciences

Investigators

• Principal Investigator: John Puskas, MD; Icahn School of Medicine at Mount Sinai

  Study Documents (Full-Text)

Documents provided by Edwards Lifesciences:

Study Protocol and Statistical Analysis Plan  [PDF] August 14, 2018

More Information

Additional Information:

New York Heart Association Classification 

Short Form Health Survey (SF-12) 

Publications of Results:

Puskas JD, Bavaria JE, Svensson LG, Blackstone EH, Griffith B, Gammie JS, Heimansohn DA, Sadowski J, Bartus K, Johnston DR, Rozanski J, Rosengart T, Girardi LN, Klodell CT, Mumtaz MA, Takayama H, Halkos M, Starnes V, Boateng P, Timek TA, Ryan W, Omer S, Smith CR; COMMENCE Trial Investigators. The COMMENCE trial: 2-year outcomes with an aortic bioprosthesis with RESILIA tissue. Eur J Cardiothorac Surg. 2017 Sep 1;52(3):432-439. doi: 10.1093/ejcts/ezx158.

Johnston DR, Griffith BP, Puskas JD, Bavaria JE, Svensson LG; COMMENCE Trial Investigators. Intermediate-term outcomes of aortic valve replacement using a bioprosthesis with a novel tissue. J Thorac Cardiovasc Surg. 2020 Feb 21. pii: S0022-5223(20)30474-8. doi: 10.1016/j.jtcvs.2020.01.095. [Epub ahead of print]

• Responsible Party: Edwards Lifesciences
• ClinicalTrials.gov Identifier: NCT01757665
• Other Study ID Numbers: 2012-02
• First Posted: December 31, 2012
• Results First Posted: December 27, 2019
• Last Update Posted: January 25, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Edwards Lifesciences:

Aortic valve replacement; Mitral valve replacement

Additional relevant MeSH terms:

Aortic Valve Stenosis; Mitral Valve Insufficiency; Aortic Valve Insufficiency; Mitral Valve Stenosis; Constriction, Pathologic; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Valve Diseases; Ventricular Outflow Obstruction