The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633 AM1)(TERMINATED)
Condition: Coronary Artery Bypass; Myocardial Infarction; Ventricular Dysfunction, Left; Stroke; Cardiopulmonary Bypass
MeSH terms: Myocardial Infarction; Ventricular Dysfunction; Ventricular Dysfunction, Left; Infarction
Intervention: Acadesine; Normal Saline
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.; 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3080.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

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.
    

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