Document Detail


Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial.
MedLine Citation:
PMID:  22782417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery.
OBJECTIVE: To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days.
DESIGN, SETTING, AND PARTICIPANTS: The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010.
INTERVENTIONS: Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction.
MAIN OUTCOME MEASURE: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28.
RESULTS: Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured.
CONCLUSION: In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00872001.
Authors:
Mark F Newman; T Bruce Ferguson; Jennifer A White; Giuseppe Ambrosio; Joerg Koglin; Nancy A Nussmeier; Ronald G Pearl; Bertram Pitt; Andrew S Wechsler; Richard D Weisel; Tammy L Reece; Armando Lira; Robert A Harrington;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA     Volume:  308     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-11     Completed Date:  2012-07-12     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  157-64     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00872001
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MeSH Terms
Descriptor/Qualifier:
Adenosine / metabolism*
Aged
Aminoimidazole Carboxamide / adverse effects,  analogs & derivatives*,  therapeutic use
Coronary Artery Bypass / adverse effects*,  methods,  mortality*
Coronary Artery Disease / surgery
Double-Blind Method
Female
Humans
Male
Middle Aged
Perioperative Period
Reperfusion Injury / prevention & control*
Ribonucleosides / adverse effects,  therapeutic use*
Stroke
Ventricular Dysfunction, Left
Chemical
Reg. No./Substance:
0/Ribonucleosides; 360-97-4/Aminoimidazole Carboxamide; 53IEF47846/acadesine; K72T3FS567/Adenosine
Investigator
Investigator/Affiliation:
Giuseppe Ambrosio / ; T Bruce Ferguson / ; Robert A Harrington / ; Joerg Koglin / ; Mark F Newman / ; Nancy Nussmeier / ; Ronald G Pearl / ; Bertram Pitt / ; Andrew S Wechsler / ; Richard D Weisel / ; Stephen Fremes / ; Philippe Menasché / ; Friedrich Wilhelm Mohr / ; Ardawan J Rastan / ; Axel Haverich / ; Ugolino Livi / ; Pieter Kappetein / ; Gonzalo Pradas / ; Robert A Harrington / ; Mark F Newman / ; Elliott Bennett-Guerrero / ; T Bruce Ferguson / ; Linda Mongero / ; Xing Li Wang / ; John H Alexander / ; Davy Cheng / ; Frederick L Grover / ; Yuliya Lokhnygina / ; Hans-Christoph Diener /
Comments/Corrections
Comment In:
Nat Rev Cardiol. 2012 Sep;9(9):493   [PMID:  22847168 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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