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

NCT ID: NCT00872001

Last Updated: 2015-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 3080 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2010-10-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Acadesine

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

Group Type: ACTIVE_COMPARATOR

Acadesine

Intervention Type: DRUG

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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

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.

Interventions

Acadesine

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

Normal Saline

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.

Intervention Type: DRUG

Other Intervention Names

SCH 900395

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke Clinical Research Institute

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: DERIVED

PMID: 25218533 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22782417 (View on PubMed)

Other Identifiers

MK-8395

Identifier Type: OTHER

Identifier Source: secondary_id

RED-CABG

Identifier Type: OTHER

Identifier Source: secondary_id

P05633

Identifier Type: -

Identifier Source: org_study_id