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

This study has been terminated.
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00872001
First received: March 27, 2009
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Coronary Artery Bypass
Myocardial Infarction
Ventricular Dysfunction, Left
Stroke
Cardiopulmonary Bypass
Drug: Acadesine
Drug: Normal Saline
Phase 3

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:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Incidence of All-cause Death, Non-fatal Stroke, and Need for Mechanical Support for Severe Left Ventricular Dysfunction (SLVD) (Intent-to-Treat Population) [ Time Frame: Up to Post-Operative Day 28 ] [ Designated as safety issue: No ]
    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:
  • Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population) [ Time Frame: Up to Post-Operative Day 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 3080
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 intravenous (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 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, 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
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00872001     History of Changes
Other Study ID Numbers: P05633, MK-8395, RED-CABG
Study First Received: March 27, 2009
Results First Received: November 20, 2012
Last Updated: October 24, 2013
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
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on September 11, 2014