Schering-Plough Corporation today announced the start of patient enrollment in RED-CABG, the Phase 3 Trial for acadesine, an investigational, potentially first-in-class adenosine regulating agent (ARA). Acadesine was licensed from PeriCor Therapeutics, Inc., a privately held specialty biopharmaceutical company.
Acadesine is being studied as intravenous infusion for the prevention of ischemia-reperfusion injury, a complication of cardiac surgery in patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (a procedure that stops the heart and places the patient on a pump).
"Ischemia-reperfusion injury represents a serious and life-threatening cardiac surgery complication in patients undergoing coronary artery bypass surgery performed with cardiopulmonary bypass, and there are currently no approved treatments," stated Robert Harrington, M.D., Director of the Duke Clinical Research Institute, and Study Chair of the trial.
Although CABG surgical techniques have improved and reduced procedural morbidity and mortality, complication rates resulting from these procedures, such as ischemia-reperfusion injury, remain unacceptably high. According to a national cardiac surgery database from the Society of Thoracic Surgeons, there is a 30-day operative mortality and major complication rate of 13.4 percent associated with the CABG procedure. In addition, an agent that can be shown to reduce surgical complications can potentially have a significant impact on healthcare costs.
"We are pleased to be initiating the RED-CABG Phase 3 clinical trial for acadesine, which has the potential to reduce perioperative complications in patients undergoing CABG surgery," Enrico Veltri, M.D., Group Vice President, Global Clinical Research, Cardiovascular and Metabolic Diseases, Schering-Plough Research Institute. "Schering-Plough is committed to addressing the significant unmet medical need in ischemia-reperfusion injury in this patient population," he added.
CABG and Reperfusion Injury
CABG surgery is a recommended treatment for high-risk patients who have coronary artery disease or previously experienced an ischemic event, such as a myocardial infarction (heart attack) or unstable angina, according to the guidelines of the American Heart Association and the American College of Cardiology.
Ischemia-reperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood creates a condition in which restoration of circulation results in inflammation and oxidative damage rather than restoration of normal function.
The RED-CABG Phase 3 Trial
The RED-CABG (Reduction in cardiovascular Events by acaDesine in subjects undergoing CABG) Trial is a randomized, double-blind, placebo-controlled, multinational, Phase 3 study of 7500 high-risk patients undergoing on-pump CABG. High-risk patients are defined as either female, or males with a previous history of CABG surgery, heart attack, stroke, low left ventricular ejection fraction, or diabetes mellitus. Patients will be randomized to either acadesine or placebo IV infusion started before anesthesia and continued for a total of seven hours through surgery and postoperatively. The primary endpoint is a composite of all-cause death, severe left ventricular dysfunction requiring mechanical support, or stroke at post-operative day 28. All-cause death will also be assessed at six months.