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Original Contribution
July 11, 2012

Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting: The RED-CABG Randomized Controlled Trial

Author Affiliations

Author Affiliations: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina (Drs Newman and Harrington and Mss White and Reece); Department of Cardiovascular Sciences, East Carolina Heart Institute, Greenville, North Carolina (Dr Ferguson); University of Perugia School of Medicine, Perugia, Italy (Dr Ambrosio); Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey (Drs Koglin and Lira); SUNY Upstate Medical University, Syracuse, New York (Dr Nussmeier); Stanford University School of Medicine, Palo Alto, California (Dr Pearl); University of Michigan School of Medicine, Ann Arbor (Dr Pitt); Drexel University College of Medicine, Philadelphia, Pennsylvania (Dr Wechsler); and the University Health Network, Toronto, Ontario, Canada (Dr Weisel).

JAMA. 2012;308(2):157-164. doi:10.1001/jama.2012.7633
Abstract

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

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