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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Coronary Artery Bypass, Myocardial Infarction, Ventricular Dysfunction, Left, Stroke, Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: Acadesine
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acadesine<br>Acadesine intravenous (IV) infusion, plus cardioplegia solution with acadesine, and priming solution with acadesine in the heart lung machine during cardiopulmonary bypass (CPB) | Drug: Acadesine<br>* 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.<br>* Other names: SCH 900395;|
| Placebo Comparator: Placebo<br>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 | Drug: Normal Saline<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Post-Operative Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Post-Operative Day 28 |