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.