Clinical trial NCT00872001: The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633 AM1)(TERMINATED)
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronary Artery Bypass
Myocardial Infarction
Ventricular Dysfunction, Left
Stroke
Cardiopulmonary Bypass
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
First posted: 2009-03-30
Enrollment: 3080
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Incidence of All-cause Death, Non-fatal Stroke, and Need for Mechanical Support for Severe Left Ventricular Dysfunction (SLVD) (Intent-to-Treat Population)
timeFrame: Up to Post-Operative Day 28
Secondary outcomes:
measure: Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population)
timeFrame: Up to Post-Operative Day 28
Other outcomes:
Locations:
Study officials:
References:
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.
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.