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

Phase 3

Terminated

• Conditions: Coronary Artery Bypass; Cardiopulmonary Bypass; Stroke; Myocardial Infarction; Ventricular Dysfunction, Left
• Interventions: Drug: Acadesine; Drug: Normal Saline

• Registration Number: NCT00872001
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-03-27
• Study First Submitted QC: 2009-03-27
• Study First Posted: 2009-03-30
• Study Start: 2009-04
• Primary Completion: 2010-10
• Study Completion: 2010-10
• Results First Submitted: 2012-11-20
• Results First Submitted QC: 2012-11-20
• Results First Posted: 2012-12-20
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-28
• Last Update Posted: 2015-10-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3080

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acadesine	Acadesine	Acadesine intravenous (IV) infusion, plus cardioplegia solution with acadesine, and priming solution with acadesine in the heart lung machine during cardiopulmonary bypass (CPB)
Placebo	Normal Saline	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

Primary Outcome Measures

Name	Time	Method
Incidence of All-cause Death, Non-fatal Stroke, and Need for Mechanical Support for Severe Left Ventricular Dysfunction (SLVD) (Intent-to-Treat Population)	Up to Post-Operative Day 28	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

Name	Time	Method
Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population)	Up to Post-Operative Day 28	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.