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

ProspeCtive, nOn-randoMized, MulticENter Clinical Evaluation of Edwards Pericardial Aortic and Mitral Bioprostheses (Models 11000A and 11000M) With a New Tissue Treatment Platform (COMMENCE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Aortic Stenosis; Mitral Valve Insufficiency; Aortic Valve Insufficiency; Mitral Stenosis
• Intervention / Treatment: Device: Edwards Aortic and Mitral Bioprostheses Models 11000A and 11000M

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 Type: Interventional
• Enrollment (Actual): 777
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• Poland
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Warsaw, Poland, 04-628
    • The Cardinal Stefan Wyszynski Institute of Cardiology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology, P.C.
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Sacramento, California, United States, 95919
      • Sutter Institute for Medical Research
    • Stanford, California, United States, 94305
      • Board of Trustees of the Leland Stanford Junior University
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale-New Haven
  • Florida
    • Gainesville, Florida, United States, 32608
      • Shands at the University of Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Heart Center of Indiana
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospital
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 36131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University/ Barnes Jewish Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital - Columbia University Medical Center
    • New York, New York, United States, 10025
      • Mount Sinai Morningside
    • New York, New York, United States, 10021
      • New York Weill Cornell Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Columbus, Ohio, United States, 43124
      • OhioHealth Research Institute
  • Pennsylvania
    • Mechanicsburg, Pennsylvania, United States, 17050
      • Pinnacle Health Cardiovascular Institute
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Health
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • Plano, Texas, United States, 75093
      • The Heart Hospital of Baylor Plano
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

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

Description

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

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects With Structural Valve Deterioration	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.	1 Year Post Implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Early Adverse Events	Number of subjects with early adverse events occurring within 30 days of procedure divided by the number of enrolled subjects times 100	Events occuring within 30 days of procedure
Percentage of Late Adverse Events Divided by Late Patient Years	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).	Events occurring >= 31 days and up through 3 years post-implant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject's Average Mean Gradient Measurements - 11000A	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.	3 Months, 1 Year, and 2 Year Post Implant
Subject's Average Mean Gradient Measurements - 11000M	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 Months, 1 Year, and 2 Years Post Implant
Subject's Average Peak Gradients Measurements Over Time - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Peak Gradients Measurements Over Time - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Effective Orifice Area Measurements - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Effective Orifice Area Measurements - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Effective Orifice Area Index (EOAI) Measurements - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Effective Orifice Area Index (EOAI) Measurements - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Performance Index Measurements - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Performance Index Measurements - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Cardiac Output Over Time - 11000A	The amount of blood the heart pumps through the circulatory system in a minute.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Cardiac Output Over Time - 11000M	The amount of blood the heart pumps through the circulatory system in a minute.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Cardiac Index Over Time- 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Cardiac Index Over Time - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Amount of Total Valvular Regurgitation Over Time - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Amount of Total Valvular Regurgitation Over Time - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Amount of Paravalvular Leak Over Time - 11000A	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Amount of Paravalvular Leak Over Time - 11000M	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's New York Heart Association (NYHA) Functional Class Compared to Baseline	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.	3 Months, 1 Year, and 2 Years Post Implant
Subject's Average Score at Baseline and 1 Year on the Quality of Life Survey	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.	Baseline and one year post-implant
Subject's Average White Blood Cell Count	Laboratory analysis of White Blood Cell (WBC) count on blood drawn from subject; WBC fight infection.	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Red Blood Cells Count	Laboratory Analysis of Red Blood Cell (RBC) Count on blood drawn from subjects; RBC carry oxygen.	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Hematocrit Percentage	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).	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Hemoglobin Count	Laboratory Analysis of Hemoglobin Count on blood drawn from subjects. Hemoglobin is an oxygen-carrying protein in red blood cells.	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Platelet Count	Laboratory Analysis of Platelet Count on blood drawn from subjects; platelets help with blood clotting.	Baseline, Discharge, 3 Months, 1 Year, and 2 Years
Subject's Average Plasma Free Hemoglobin	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).	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average International Normalized Ratio	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.	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Partial Thromboplastin Time	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.	Baseline, Discharge, 3 Months, 1 Year and 2 Year
Subject's Average Prothrombin Time	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.	Baseline, Discharge, 3 Months, 1 Year, and 2 Years
Subjects Average Serum Glycerol Levels	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).	Pre-Implant (post-heparinization) and Post-Implant (between 60 and 120 minutes after heart was restarted)

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: John Puskas, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• 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. 2021 Nov;162(5):1478-1485. doi: 10.1016/j.jtcvs.2020.01.095. Epub 2020 Feb 21.
• Bavaria JE, Griffith B, Heimansohn DA, Rozanski J, Johnston DR, Bartus K, Girardi LN, Beaver T, Takayama H, Mumtaz MA, Rosengart TK, Starnes V, Timek TA, Boateng P, Ryan W, Cornwell LD, Blackstone EH, Borger MA, Pibarot P, Thourani VH, Svensson LG, Puskas JD; COMMENCE Trial Investigators. Five-year Outcomes of the COMMENCE Trial Investigating Aortic Valve Replacement With RESILIA Tissue. Ann Thorac Surg. 2023 Jun;115(6):1429-1436. doi: 10.1016/j.athoracsur.2021.12.058. Epub 2022 Jan 20.
• Heimansohn DA, Baker C, Rodriguez E, Takayama H, Dagenais F, Talton DS, Mumtaz MA, Pibarot P, Puskas JD; COMMENCE Trial Investigators. Mid-term outcomes of the COMMENCE trial investigating mitral valve replacement using a bioprosthesis with a novel tissue. JTCVS Open. 2023 Jun 2;15:151-163. doi: 10.1016/j.xjon.2023.05.008. eCollection 2023 Sep.
• Beaver T, Bavaria JE, Griffith B, Svensson LG, Pibarot P, Borger MA, Sharaf OM, Heimansohn DA, Thourani VH, Blackstone EH, Puskas JD; COMMENCE Trial Investigators. Seven-year outcomes following aortic valve replacement with a novel tissue bioprosthesis. J Thorac Cardiovasc Surg. 2023 Sep 29:S0022-5223(23)00873-5. doi: 10.1016/j.jtcvs.2023.09.047. Online ahead of print.

Helpful Links

• New York Heart Association Classification

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2012
• Primary Completion (Actual): August 1, 2017
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 18, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimated): December 31, 2012

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Mitral valve replacement; Aortic valve replacement
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Mitral Valve Insufficiency; Aortic Valve Insufficiency; Constriction, Pathologic; Mitral Valve Stenosis
• Other Study ID Numbers: 2012-02 (AP HM)

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