A Phase II Multicenter Double-Blind Placebo-Controlled Study of Ethyl Pyruvate in High-Risk Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

作者：Bennett Guerrero Elliott^*; Swaminathan Madhav; Grigore Alina M; Roach Gary W; Aberle Laura G; Johnston Jeffrey M; Fink Mitchell P

来源：Journal of Cardiothoracic and Vascular Anesthesia, 2009, 23(3): 324-329.

DOI：10.1053/j.jvca.2008.08.005

• phase II
• human
• ethyl pyruvate
• cardiopulmonary bypass
• cardiac surgery

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.

• 出版日期2009-6