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The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633 AM1)(TERMINATED) (RED-CABG)

Primary Purpose

Coronary Artery Bypass, Myocardial Infarction, Ventricular Dysfunction, Left

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Acadesine
Normal Saline
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Coronary Artery Bypass

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • A high risk participant undergoing non emergency CABG surgery requiring CPB and cardioplegia.
  • Age: >=50 years

  • At least one of the following risk factors:

    • Female (but not pregnant or lactating), or
    • History of prior CABG, or
    • History of myocardial infarction (MI), or
    • History of ischemic stroke, or
    • Left ventricular ejection fraction <=30%, or
    • Diabetes mellitus requiring insulin and/or antidiabetic agents.
  • Significant coronary artery stenosis

Exclusion Criteria:

  • Planned valve replacement, carotid artery or aortic surgery, distal coronary endarterectomy,surgical ablation for cardiac arrhythmia, or ventricular aneurysmectomy, alone or with CABG surgery (repair for mild to moderate mitral valve disease with concomitant CABG is not excluded).
  • Planned or staged major surgery within 30 days of CABG surgery
  • CABG surgery using intermittent aortic cross clamping without cardioplegia.
  • Minimally invasive surgery (ie, without use of CPB).
  • MI within 5 days prior to surgery.
  • Pre-operative or planned intra operative/postoperative use of intra-aortic balloon pump (IABP), ventricular assist device (VAD), extra-corporeal membrane oxygenator (ECMO), or other mechanical hemodynamic assist device.
  • History or presence of gout or uric acid nephrolithiasis.
  • Serum creatinine >2 mg/dL (180 µmol/L).
  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x Upper Limit of Normal (ULN).
  • Adenosine, aminophylline, nicotinic acid, pentoxifylline, theophylline, and any cardioplegia solution containing adenosine, dipyridamole or lidoflazine within 24 hours before surgery:
  • Dipyridamole within 2 days and allopurinol or febuxostat within 4 days before surgery
  • Food and drinks containing caffeine, theobromines or methylxanthines (such as coffee, tea, colas, some 'energy' drinks or chocolate) within 12 hours before surgery.
  • Pregnancy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Acadesine

    Placebo

    Arm Description

    Acadesine intravenous (IV) infusion, plus cardioplegia solution with acadesine, and priming solution with acadesine in the heart lung machine during cardiopulmonary bypass (CPB)

    Normal saline, IV infusion, plus cardioplegia solution with added normal saline, and priming solution with added normal saline in the heart lung machine during CPB

    Outcomes

    Primary Outcome Measures

    Incidence of All-cause Death, Non-fatal Stroke, and Need for Mechanical Support for Severe Left Ventricular Dysfunction (SLVD) (Intent-to-Treat Population)
    Incidence of all-cause death, non-fatal stroke, or need for mechanical support for SLVD (any component and composite) through post-operative Day 28 during and following CABG and administration of acadesine or placebo. Components defined as follows: All-cause death: Death from any cause, Non-fatal Stoke: occurrence of a stoke that was confirmed and adjudicated by Clinical Endpoints Committee that did not result in death, and Mechanical Support for SLVD: New use of any mechanical support for ≥1 hour for treatment of low cardiac output.

    Secondary Outcome Measures

    Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population)
    Incidence of cardiovascular death, non-fatal stroke, and need for mechanical support for SLVD (any component and composite) through post-operative Day 28 during and following CABG and administration of acadesine or placebo. Components defined as follows: Cardiovascular death: Death due to cardiovascular causes, Non-fatal Stroke: occurrence of a stroke that was confirmed and adjudicated by Clinical Endpoints Committee that did not result in death, and Mechanical Support for SLVD: New use of any mechanical support for ≥1 hour for treatment of low cardiac output.

    Full Information

    First Posted
    March 27, 2009
    Last Updated
    October 28, 2015
    Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Duke Clinical Research Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00872001
    Brief Title
    The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633 AM1)(TERMINATED)
    Acronym
    RED-CABG
    Official Title
    The Effect Of Acadesine On Clinically Significant Adverse Cardiovascular and Cerebrovascular Events In High-Risk Subjects Undergoing Coronary Artery Bypass Graft (CABG) Surgery Using Cardiopulmonary Bypass (Protocol No. P05633): RED-CABG Trial (Reduction in Cardiovascular Events by AcaDesine in Subjects Undergoing CABG)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2015
    Overall Recruitment Status
    Terminated
    Study Start Date
    April 2009 (undefined)
    Primary Completion Date
    October 2010 (Actual)
    Study Completion Date
    October 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Duke Clinical Research Institute

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to determine whether acadesine is effective in reducing the cardiovascular and cerebrovascular adverse events in high-risk participants undergoing CABG surgery.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Coronary Artery Bypass, Myocardial Infarction, Ventricular Dysfunction, Left, Stroke, Cardiopulmonary Bypass

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    3080 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Acadesine
    Arm Type
    Active Comparator
    Arm Description
    Acadesine intravenous (IV) infusion, plus cardioplegia solution with acadesine, and priming solution with acadesine in the heart lung machine during cardiopulmonary bypass (CPB)
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Normal saline, IV infusion, plus cardioplegia solution with added normal saline, and priming solution with added normal saline in the heart lung machine during CPB
    Intervention Type
    Drug
    Intervention Name(s)
    Acadesine
    Other Intervention Name(s)
    SCH 900395
    Intervention Description
    Acadesine 42 mg/kg diluted in normal saline to a total of 500 mL, delivered as an IV infusion over approximately 7 hours commencing within approximately 30 minutes before induction of anesthesia at a rate of 0.1 mg/kg/min (translating into 1.2 mL/min for a 500 mL solution). In addition, a 5 µg/mL cardioplegia solution of acadesine will be administered, and acadesine will be added to the priming solution (5 µg/mL) in the heart lung machine during CPB.
    Intervention Type
    Drug
    Intervention Name(s)
    Normal Saline
    Intervention Description
    Normal saline, 500 mL delivered as an IV infusion over approximately 7 hours commencing within approximately 30 minutes before induction of anesthesia at a rate of 1.2 mL/min for a 500 mL solution. In addition, standard cardioplegia solution with added normal saline will be administered, and placebo (normal saline) will also be added to the heart lung machine priming solution.
    Primary Outcome Measure Information:
    Title
    Incidence of All-cause Death, Non-fatal Stroke, and Need for Mechanical Support for Severe Left Ventricular Dysfunction (SLVD) (Intent-to-Treat Population)
    Description
    Incidence of all-cause death, non-fatal stroke, or need for mechanical support for SLVD (any component and composite) through post-operative Day 28 during and following CABG and administration of acadesine or placebo. Components defined as follows: All-cause death: Death from any cause, Non-fatal Stoke: occurrence of a stoke that was confirmed and adjudicated by Clinical Endpoints Committee that did not result in death, and Mechanical Support for SLVD: New use of any mechanical support for ≥1 hour for treatment of low cardiac output.
    Time Frame
    Up to Post-Operative Day 28
    Secondary Outcome Measure Information:
    Title
    Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population)
    Description
    Incidence of cardiovascular death, non-fatal stroke, and need for mechanical support for SLVD (any component and composite) through post-operative Day 28 during and following CABG and administration of acadesine or placebo. Components defined as follows: Cardiovascular death: Death due to cardiovascular causes, Non-fatal Stroke: occurrence of a stroke that was confirmed and adjudicated by Clinical Endpoints Committee that did not result in death, and Mechanical Support for SLVD: New use of any mechanical support for ≥1 hour for treatment of low cardiac output.
    Time Frame
    Up to Post-Operative Day 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: A high risk participant undergoing non emergency CABG surgery requiring CPB and cardioplegia. Age: >=50 years At least one of the following risk factors: Female (but not pregnant or lactating), or History of prior CABG, or History of myocardial infarction (MI), or History of ischemic stroke, or Left ventricular ejection fraction <=30%, or Diabetes mellitus requiring insulin and/or antidiabetic agents. Significant coronary artery stenosis Exclusion Criteria: Planned valve replacement, carotid artery or aortic surgery, distal coronary endarterectomy,surgical ablation for cardiac arrhythmia, or ventricular aneurysmectomy, alone or with CABG surgery (repair for mild to moderate mitral valve disease with concomitant CABG is not excluded). Planned or staged major surgery within 30 days of CABG surgery CABG surgery using intermittent aortic cross clamping without cardioplegia. Minimally invasive surgery (ie, without use of CPB). MI within 5 days prior to surgery. Pre-operative or planned intra operative/postoperative use of intra-aortic balloon pump (IABP), ventricular assist device (VAD), extra-corporeal membrane oxygenator (ECMO), or other mechanical hemodynamic assist device. History or presence of gout or uric acid nephrolithiasis. Serum creatinine >2 mg/dL (180 µmol/L). Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x Upper Limit of Normal (ULN). Adenosine, aminophylline, nicotinic acid, pentoxifylline, theophylline, and any cardioplegia solution containing adenosine, dipyridamole or lidoflazine within 24 hours before surgery: Dipyridamole within 2 days and allopurinol or febuxostat within 4 days before surgery Food and drinks containing caffeine, theobromines or methylxanthines (such as coffee, tea, colas, some 'energy' drinks or chocolate) within 12 hours before surgery. Pregnancy

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    25218533
    Citation
    Weisel RD, Nussmeier N, Newman MF, Pearl RG, Wechsler AS, Ambrosio G, Pitt B, Clare RM, Pieper KS, Mongero L, Reece TL, Yau TM, Fremes S, Menasche P, Lira A, Harrington RA, Ferguson TB; RED-CABG Executive and Steering Committees. Predictors of contemporary coronary artery bypass grafting outcomes. J Thorac Cardiovasc Surg. 2014 Dec;148(6):2720-6.e1-2. doi: 10.1016/j.jtcvs.2014.08.018. Epub 2014 Aug 14.
    Results Reference
    derived
    PubMed Identifier
    22782417
    Citation
    Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA, Pearl RG, Pitt B, Wechsler AS, Weisel RD, Reece TL, Lira A, Harrington RA; RED-CABG Steering Committee and Investigators. Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. JAMA. 2012 Jul 11;308(2):157-64. doi: 10.1001/jama.2012.7633.
    Results Reference
    derived

    Learn more about this trial

    The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633 AM1)(TERMINATED)

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