Inhibition of Lipid Peroxidation During Cardiac Surgery
2015年1月14日 更新者:Mias Pretorius、Vanderbilt University
Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB).
Hemolysis and rhabdomyolysis frequently occur during CPB.
Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin.
Free plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute kidney injury that results from CPB.
When these hemeproteins are released into the plasma, they undergo redox cycling, generating radical species that initiate lipid peroxidation and a cascade of oxidative damage to cellular membranes, notably in the kidney.
F2-isoprostanes and isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased after CPB, particularly in those patients with acute kidney injury.
Acetaminophen inhibits the lipid peroxidation catalyzed by myoglobin and hemoglobin.
Moreover, in an animal model of rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in creatinine clearance compared to control.
The current proposal tests the central hypothesis that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and rhabdomyolysis that occur in patients undergoing CPB.
Demonstration that acetaminophen inhibits the lipid peroxidation resulting from CPB would provide a rationale for a prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute kidney injury that results from CPB.
研究概览
研究类型
介入性
注册 (实际的)
67
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
Tennessee
-
Nashville、Tennessee、美国、37232
- Vanderbilt University Medical Center
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
- For female subjects, the following conditions must be met:
postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and a negative urine beta-hcg prior to drug treatment
Exclusion Criteria:
- Allergic reaction to ApAP (acetaminophen)
- Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
- Impaired renal function (serum creatinine >2.0 mg/dl)
- Emergency surgery
- Pregnancy
- Breast-feeding
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
- History of alcohol or drug abuse
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
- History or evidence of active asthma
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
安慰剂比较:安慰剂
|
Acetaminophen 1g every 6 hours for 4 doses over 24 hours
其他名称:
|
有源比较器:Acetaminophen
Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period
|
Acetaminophen 1g every 6 hours for 4 doses over 24 hours
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Plasma Isofuran Concentrations
大体时间:24 hours
|
Plasma isofuran concentrations as a measure of lipid peroxidation
|
24 hours
|
Plasma F2-isoprostane Concentrations
大体时间:24 hours
|
Plasma F2-isoprostane concentrations as a measure of lipid peroxidation
|
24 hours
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)
大体时间:24 hours
|
Changes in urinary NGAL (neutrophil gelatinase-associated lipocalin) as marker of acute kidney injury
|
24 hours
|
Serum Creatinine
大体时间:72 hours
|
Serum creatinine measured over a 72 hour period
|
72 hours
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Mias Pretorius, MBChB, MSCI、Vanderbilt University
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, Carney CK, Masterson TS, Amin T, Wright DW, Wilson MT, Oates JA, Roberts LJ 2nd. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2699-704. doi: 10.1073/pnas.0910174107. Epub 2010 Feb 1.
- Billings FT 4th, Ball SK, Roberts LJ 2nd, Pretorius M. Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response. Free Radic Biol Med. 2011 Jun 1;50(11):1480-7. doi: 10.1016/j.freeradbiomed.2011.02.011. Epub 2011 Feb 18.
- Billings FT 4th, Petracek MR, Roberts LJ 2nd, Pretorius M. Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial. PLoS One. 2015 Feb 23;10(2):e0117625. doi: 10.1371/journal.pone.0117625. eCollection 2015.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2011年7月1日
初级完成 (实际的)
2013年6月1日
研究完成 (实际的)
2013年6月1日
研究注册日期
首次提交
2011年6月2日
首先提交符合 QC 标准的
2011年6月3日
首次发布 (估计)
2011年6月6日
研究记录更新
最后更新发布 (估计)
2015年1月27日
上次提交的符合 QC 标准的更新
2015年1月14日
最后验证
2015年1月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.