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

NCT00872001 | Terminated Phase 3 Results DMC

• 3 other identifiers: P05633MK-8395RED-CABG
• Study Type: interventional
• Target: 3,080
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Incidence of Cardiovascular Death, Non-fatal Stroke, and Need for Mechanical Support for SLVD (Intent-to-Treat Population)

  Up to Post-Operative Day 28

Study Arms (2)

Acadesine

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Acadesine 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.

Also known as: SCH 900395

Acadesine

Normal Saline 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.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Duke Clinical Research Institute: collaborator

Related Publications (2)

• 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.

  PMID: 25218533 DERIVED

• 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.

  PMID: 22782417 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Ventricular Dysfunction, Left; Stroke

Interventions

acadesine; Saline Solution

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Ventricular Dysfunction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2009
• First Posted: March 30, 2009
• Study Start: April 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 29, 2015
• Results First Posted: December 20, 2012

Record last verified: 2015-10