Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia (DREAM)
2013年2月13日 更新者:Willem-Peter Theodoor Ruifrok、University Medical Center Groningen
An Open Label Study to Evaluate the Effect of Intravenous Erythropoietin on Erythropoietin Receptor Signaling and Markers for Apoptosis, Myocardial Damage and Renal Dysfunction in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery
This is a phase 2 study that evaluates the effect of intravenous administration of a bolus EPO on the activation of EPOR-signal transduction cascades and myocardial apoptosis during cardiopulmonary bypass surgery.
Human atrial and ventricular tissue will be collected during CABG surgery for 3-vessel disease for the assay of EPOR signaling and apoptosis.
Two atrial specimens will be collected before and at the end of cardiopulmonary bypass (CPB).
Concomitantly, two transmural ventricular biopsies will be obtained, at the start and at the end of CPB.
Immediately after obtaining the first atrial biopsy, one bolus of EPO will be administered intravenously.
The atrial tissue will be split and appropriate sections will be frozen for determination of baseline expression or activity of a number of molecules including Erk1/2, STAT5, Akt and caspase-3 or embedded in paraffin for immunohistochemistry. Ventricular tissue will only be processed for immunohistochemistry. Additionally, plasma will be collected before the procedure and for up to 30 days post-procedure to examine release of markers of both myocardial ischemia and stress (CK-MB, Troponin T and NT-proBNP) and renal dysfunction (cystatin C, creatinine for eGFR).
Before initializing the randomised study, a pilot study will be performed with 5 subjects that will not be treated to evaluate the feasibility of myocardial sample collection.
Initiation of the randomised study will only commence if baseline activity of EPOR-STC can be determined in the atrial tissue and caspase-3 positive cells can be identified in the second ventricular biopsy.
研究概览
研究类型
介入性
注册 (实际的)
10
阶段
- 阶段2
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
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Groningen、荷兰、9700 BD
- University Medical Center Groningen, Dept. of Cardiology
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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:
- Before any study-specific procedure, including assessments for screening, the appropriate written informed consent must be obtained.
- Man or woman 18 to 80 years of age .
- Undergoing a planned, elective cardiopulmonary bypass operation for the first time for 3-vessel coronary artery disease with an anticipated aortic cross clamp time of approximately 40 minutes and a total bypass time of approximately 90 minutes.
- Hemoglobin (Hb) concentration ≥7.4 mmol/l and ≤9.9 mmol/l within 7 days prior to CABG surgery and no major acute blood loss since this Hb determination.
Exclusion Criteria:
- An unstable medical condition, defined as having been hospitalized for a non-cardiac condition within 4 weeks of screening, major surgery within 24 weeks of screening, or otherwise unstable in the judgment of the investigator (e.g., at risk of complications or adverse events unrelated to study participation).
- Left ventricular ejection fraction (LVEF) < 40%.
- Clinical history of chronic kidney disease (CKD) (at any point prior to registration) defined as serum creatinine >105 μmol/l for all females, >130 μmol/l for black males, and >115 μmol/l for non-black males.
- Atrial fibrillation, paroxysmal atrial fibrillation or atrial flutter.
- Clinically significant abnormality in chemistry, hematology, or urinalysis parameters performed within the screening period.
- Current symptoms of polyurea, polydipsia, or increased thirst.
- Grand mal seizure within 1 year of enrollment.
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 105 mmHg on day of CABG surgery.
- Use of any erythropoietic protein (e.g., rHuEPO; Procrit®, Eprex®, Neorecormon®, Epogen®, Aranesp®) within 12 weeks of enrolment.
- Positive pregnancy test or known to be pregnant at the time of screening.
- Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report.
- Severe uncorrected valvular disease (including pulmonary and tricuspid) or left ventricular outflow obstruction which, in the opinion of the investigator, requires surgery.
- Pulmonary hypertension, defined as a pulmonary artery pressure > 30 mmHg at rest.
- Participation in any investigational device or drug trial(s) or receiving other investigational agent(s) within 30 days.
- Known positive for HIV antibodies, hepatitis B surface antigen, or hepatitis C antibodies.
- Any condition (e.g., unsuitable anatomy of the atrium; psychiatric illness; etc.) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
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:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:1
25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural.
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A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.
其他名称:
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安慰剂比较:2
25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural.
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A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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The increase from baseline between EPO and saline treated subjects in activity of EPOR-STC including but not limited to, phospho Erk1/2, phospho Akt, activated caspase-3, and activated STAT5 in the second atrial biopsy.
大体时间:2 hours
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2 hours
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次要结果测量
结果测量 |
大体时间 |
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Difference in apoptosis between atrial and ventricular specimens at the end of CPB, defined as the number of TUNEL and activated caspase-3 positive cells per high power field.
大体时间:2 hours
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2 hours
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Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies.
大体时间:2 hours
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2 hours
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Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients.
大体时间:30 days
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30 days
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Subject incidence rates of adverse events.
大体时间:30 days
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30 days
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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
- 学习椅:W. H. van Gilst, Prof, dr、University Medical Center Groningen, Dept. of Exprimental Cardiology
- 首席研究员:W. T. Ruifrok, MD、University Medical Center Groningen, Dept. of Experimental Cardiology
- 首席研究员:B. D. Westenbrink, MD、University Medical Center Groningen, Dept. of Experimental Cardiology
- 首席研究员:A. H. Epema, dr, MD、University Medical Center Groningen, Dept. of Anaesthesiology
- 首席研究员:H. E. Mungroop, dr, MD、University Medical Center Groningen, Dept. of Anaesthesiology
- 首席研究员:P. W. Boonstra, Prof, dr, MD、University Medical Center Groningen, Dept. of Cardiothoracic Surgery
- 首席研究员:R. A. de Boer, dr, MD、University Medical Center Groningen, Dept of Cardiology
- 研究主任:D. J. van Veldhuisen, Prof, dr, MD、University Medical Center Groningen, Dept. of Cardiology
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。
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
2007年9月1日
初级完成 (实际的)
2011年1月1日
研究完成 (实际的)
2011年4月1日
研究注册日期
首次提交
2007年9月4日
首先提交符合 QC 标准的
2007年9月4日
首次发布 (估计)
2007年9月5日
研究记录更新
最后更新发布 (估计)
2013年2月15日
上次提交的符合 QC 标准的更新
2013年2月13日
最后验证
2013年2月1日
更多信息
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