A Phase II Multicenter Double-Blind Placebo-Controlled Study of Ethyl Pyruvate in High-Risk Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass
A Phase II Multicenter Double-Blind Placebo-Controlled Study of Ethyl Pyruvate in High-Risk Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass
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DOI：
10.1053/j.jvca.2008.08.005
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发表时间：
2009-06-01
影响因子：
2.8
通讯作者：
Fink, Mitchell P.
中科院分区：
文献类型：
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作者：
Bennett-Guerrero, Elliott;Swaminathan, Madhav;Fink, Mitchell P.
目的：丙酮酸乙酯(EP)是一种研究中的药物，已被证明在几种危重疾病模型中对动物具有保护作用，包括心肌或肠系膜缺血/再灌注损伤、败血症和失血性休克。本研究的目的是评估EP对高危心脏手术患者的安全性，并获得预防单系统和多系统器官功能障碍的初步疗效数据。设计：双盲、随机、安慰剂对照研究。地点：13家美国医院。参与者：接受冠状动脉搭桥术和/或心脏瓣膜手术的高危患者(Parsonnet Risk Score>；15)。干预：受试者被随机分为安慰剂或EP组(全麻诱导后开始静脉注射7,500 mg，然后每6小时再注射5次，共7,500 mg)。平均体重(83千克)，相当于在6个给药间隔中每一个的剂量为90毫克/千克，超过了在许多动物模型中被证明有效的40毫克/千克的剂量。测量和主要结果：主要的综合终点包括术后28天内发生的以下任何一种情况：手术后48小时内死亡，机械通气；使用所建立的步枪标准的急性肾损伤/衰竭，或术后48小时需要血管收缩药。研究对象为102例患者(安慰剂n=53，EP n=49)。在临床参数或全身炎症标志物方面，两组之间没有统计学上的显著差异。结论：尽管在许多动物模型中都有阳性结果，但EP的应用似乎并没有给接受CPB的心脏外科患者带来任何好处。(C)2009 Elsevier Inc.保留所有权利。
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 inflammationConclusion: Despite positive results in numerous animal models, the administration of EP does not appear to confer any benefit to cardiac surgical patients undergoing CPB. (C) 2009 Elsevier Inc. All rights reserved.