The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery (Study P05633AM1)(TERMINATED) - Full Text View

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00872001

Purpose

The purpose of this study is to determine whether acadesine is effective in reducing the cardiovascular and cerebrovascular adverse events in high-risk patients undergoing CABG surgery.

Condition	Intervention	Phase
Coronary Artery Bypass Myocardial Infarction Ventricular Dysfunction, Left Stroke Cardiopulmonary Bypass	Drug: Acadesine Drug: Normal Saline	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Bypass Surgery Heart Attack

Drug Information available for: Acadesine

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

The first occurrence of any component of the composite of all-cause death, non fatal stroke, and need for mechanical support for severe left ventricular dysfunction (SLVD). [ Time Frame: During CABG surgery and following CABG surgery through post-operative day (POD) 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the clinical benefit of acadesine with respect to incidence of the first occurrence of any component of the composite of cardiovascular death, non fatal stroke, and need for mechanical support for SLVD [ Time Frame: During CABG surgery and following CABG surgery through POD 28 ] [ Designated as safety issue: No ]

Estimated Enrollment:	7500
Study Start Date:	April 2009
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Acadesine Acadesine IV infusion, plus cardioplegia solution with acadesine, and priming solution with acadesine in the heart lung machine during cardiopulmonary bypass (CPB)	Drug: Acadesine Acadesine 42 mg/kg diluted in normal saline to a total of 500 mL, delivered as an intravenous (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. Other Name: SCH 900395
Placebo Comparator: Placebo (normal saline) 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	Drug: Normal Saline Placebo (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.

Arms

Assigned Interventions

Active Comparator: Acadesine

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

Drug: Acadesine

Acadesine 42 mg/kg diluted in normal saline to a total of 500 mL, delivered as an intravenous (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.

Other Name: SCH 900395

Placebo Comparator: Placebo (normal saline)

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

Drug: Normal Saline

Placebo (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.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

A high risk patient 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

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00872001 History of Changes
Other Study ID Numbers:	P05633
Study First Received:	March 27, 2009
Last Updated:	October 21, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Stroke
Ventricular Dysfunction, Left
Ventricular Dysfunction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases

Cardiovascular Diseases
Vascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cardioplegic Solutions
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012