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

Stroke Clinical Trial

— RED-CABG  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00872001
• Other study ID #: P05633
• Secondary ID: MK-8395RED-CABG
• Status: Terminated
• Phase: Phase 3
• First received: March 27, 2009
• Last updated: October 28, 2015
• Start date: April 2009
• Est. completion date: October 2010

Study information

• Verified date: October 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3080
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Duke Clinical Research Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No