A phase II multicenter double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Ethyl pyruvate (EP) is an investigational drug that has been shown to protect animals in several models of critical illness including myocardial or mesenteric ischemia/reperfusion injury, sepsis, and hemorrhagic shock. The purpose of this study was to assess the safety of EP administration to patients undergoing higher-risk cardiac surgery and to obtain preliminary efficacy data for the prevention of single and multisystem organ dysfunction.
DESIGN: Double-blind, randomized, placebo-controlled study.
SETTING: Thirteen US hospitals. PARTICIPANTS: High-risk (Parsonnet risk score >15) patients undergoing coronary artery bypass graft and/or cardiac valvular surgery with cardiopulmonary bypass.
INTERVENTIONS: Subjects were randomized to placebo or EP (7,500 mg administered intravenously starting after the induction of general anesthesia followed by 5 more doses of 7,500 mg administered every 6 hours). The mean body weight (83 kg), corresponding to a dose of 90 mg/kg at each of the 6 dosing intervals, exceeds the dose of 40 mg/kg shown to be effective in many animal models.
MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint consisted of any of the following occurring within 28 days postoperatively: death, mechanical ventilation >48 hours postoperatively, acute renal injury/failure using the established RIFLE criteria, or need for vasoconstrictors >48 hours postoperatively. One hundred two patients were studied (placebo n = 53 and EP n = 49). No statistically significant differences were observed between groups with regard to clinical parameters or markers of systemic inflammation.
CONCLUSION: Despite positive results in numerous animal models, the administration of EP does not appear to confer any benefit to cardiac surgical patients undergoing CPB.

RCT Entities:   Population Interventions Outcomes