Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery
2021年8月2日 更新者：Daniel Stromberg、University of Texas at Austin
Cardiopulmonary bypass and arrest of the heart during cardiac surgery are necessary to allow the surgeon to perform heart operations. However, these processes can cause injury to the heart which may worsen post-operative outcomes. In fact, the effects of these injuries may continue after surgery, and lead to a long-term decrease in heart function. Neonates and young infants are at particular risk for this occurrence.
While much research has been done in adults looking for medicines that might protect the heart during surgery, few studies have been conducted in neonates and young infants. The investigators are testing Dexrazoxane, which has proven to be cardio-protective in pediatric cancer patients, in the hope that it may lessen cardiac injury during and after congenital heart surgery, and thereby improve outcomes in the neonatal and young infant population.
In order to accomplish this, the investigators must first determine how Dexrazoxane can be safely administered to young children with congenital heart disease.
研究概览
详细说明
Neonates and infants undergoing heart surgery with cardiopulmonary bypass and cardioplegic arrest experience both inflammation and myocardial ischemia-reperfusion [IR] injury. These processes provoke myocardial apoptosis and oxygen free radical formation which result in cardiac injury and dysfunction. Dexrazoxane [DRZ] is a derivative of EDTA that is approved for prevention of anthracycline-related cardiotoxicity. It provides cardioprotection through reduction of toxic reactive oxygen species [ROS], and suppression of apoptosis.
The investigators propose a 12-patient pilot to determine DRZ pharmacokinetics, and to collect additional safety data in the neonatal and infant population. Efficacy of cardioprotection will not be evaluated in this preliminary investigation, though the investigators will determine postoperative time to resolution of organ failure, development of low cardiac output syndrome, length of cardiac ICU and hospital stays, laboratory indices of myocardial injury and systemic inflammation, and echocardiographic cardiac dysfunction for safety purposes, and as a run-in to the larger, randomized, placebo controlled trial. Conducting this pilot could optimize team execution of the study protocol. In addition, results could further establish the safety of DRZ in the neonatal and infant populations.
研究类型
介入性
注册 (预期的)
12
阶段
- 阶段1
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。
学习联系方式
- 姓名：Daniel Stromberg, MD
- 电话号码：512-324-3357
- 邮箱：dstromberg@austin.utexas.edu
研究联系人备份
- 姓名：Jacob Strelow, MPH
- 电话号码：757-268-2691
- 邮箱：strelow.jacob@austin.utexas.edu
学习地点
-
-
Texas
-
Austin、Texas、美国、78723
- 招聘中
- Dell Children's Medical Center of Central Texas
-
-
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
1秒 至 1年 (孩子)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- age ≤ 1 year
- open heart surgery requiring CPB and use of cardioplegia
- parent/guardian consent for study obtained
- surgery planned Monday-Friday
Exclusion Criteria:
- gestational age <36 weeks at time of enrollment
- known syndrome or genetic abnormality, except Trisomy 21
- single ventricle physiology
- concurrent enrollment in another research protocol
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：不适用
- 介入模型：单组作业
- 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：Dexrazoxane
|
Twelve enrollees will be consecutively assigned to a dosing regimen of 400 mg/m2/dose.
The medication will be administered in the operating room 30 minutes prior to starting cardiopulmonary bypass (dose #1), prior to aortic cross clamp removal (dose #2), and on the morning after surgery in the cardiac intensive care unit (dose #3).
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 |
|---|---|---|
|
血浆峰浓度 (Cmax)
大体时间：24小时
|
24小时
|
|
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Area under the plasma concentration vs time curve (AUC)
大体时间：24 hours
|
24 hours
|
|
|
Minimum plasma concentration (Cmin)
大体时间：24 hours
|
24 hours
|
|
|
Time to resolution of organ failure
大体时间：14 days
|
defined as hours to the point of being off invasive mechanical ventilation, without significant renal dysfunction [cystatin C within normal range for age, and UOP > 1 cc/kg/hr], and off significant inotropic support [defined as milrinone >0.3 mcg/kg/min, dopamine >3 mcg/kg/min, dobutamine >3 mcg/kg/min, any combination of these inotropes, or any epinephrine, norepinephrine, phenylephrine or vasopressin)] with a serum lactate <2 mmol/L.
One point will be awarded for each postoperative hour of continued organ dysfunction up to postoperative hour 336 (day 14).
A score of 360 will be assigned if organ failure is not resolved by postoperative day 14, or if the patient requires mechanical circulatory support or experiences mortality.
This variable has been chosen to allow for recognition of early drug effects, and those which might be delayed beyond the immediate postoperative period.
|
14 days
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Myocardial Injury
大体时间：7 days
|
determined by elevated serum cardiac troponin
|
7 days
|
|
Oxidative Stress
大体时间：3 days
|
measured by lipoperoxidation (serum F2 isoprostane)
|
3 days
|
|
Inflammatory activation (IL-6 and IL-10)
大体时间：3 days
|
3 days
|
|
|
Neurologic IR injury
大体时间：3 days
|
measured by serum activin A concentration
|
3 days
|
|
ICU Length of Stay
大体时间：60 days
|
60 days
|
|
|
Hospital Length of Stay
大体时间：60 days
|
60 days
|
|
|
Tei Index (via echocardiogram)
大体时间：60 days
|
the sum of the isovolumic contraction and relaxation times divided by the ejection time
|
60 days
|
|
Ventricular ejection fraction (via echocardiogram)
大体时间：60 days
|
the volumetric fraction of fluid ejected from a chamber with each contraction
|
60 days
|
|
Tissue doppler E/E' ratio (via echocardiogram)
大体时间：60 days
|
calculated as E wave divided by e' velocities
|
60 days
|
|
Composite outcome for neonatal cardiac surgery
大体时间：60 days
|
(per Graham, EM, et al) - binary variable defined as death, use of mechanical circulatory support, cardiac arrest requiring chest compressions, hepatic injury [2 times the upper limit of normal for AST or ALT], renal injury [Cr >1.5 mg/dL], or lactic acidosis [an increasing lactate >5 mmol/L in the postoperative period]
|
60 days
|
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。
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
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- Spagnuolo RD, Recalcati S, Tacchini L, Cairo G. Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes from doxorubicin-induced toxicity. Br J Pharmacol. 2011 May;163(2):299-312. doi: 10.1111/j.1476-5381.2011.01208.x.
- Hasinoff BB, Schroeder PE, Patel D. The metabolites of the cardioprotective drug dexrazoxane do not protect myocytes from doxorubicin-induced cytotoxicity. Mol Pharmacol. 2003 Sep;64(3):670-8. doi: 10.1124/mol.64.3.670.
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- Elbl L, Hrstkova H, Tomaskova I, Michalek J. Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up. Support Care Cancer. 2006 Feb;14(2):128-36. doi: 10.1007/s00520-005-0858-8. Epub 2005 Jul 21.
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- Choi HS, Park ES, Kang HJ, Shin HY, Noh CI, Yun YS, Ahn HS, Choi JY. Dexrazoxane for preventing anthracycline cardiotoxicity in children with solid tumors. J Korean Med Sci. 2010 Sep;25(9):1336-42. doi: 10.3346/jkms.2010.25.9.1336. Epub 2010 Aug 12.
- Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, Mendenhall NP, Sposto R, Chauvenet A, Schwartz CL. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol. 2007 Feb 10;25(5):493-500. doi: 10.1200/JCO.2005.02.3879.
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- Lipshultz SE, Scully RE, Lipsitz SR, Sallan SE, Silverman LB, Miller TL, Barry EV, Asselin BL, Athale U, Clavell LA, Larsen E, Moghrabi A, Samson Y, Michon B, Schorin MA, Cohen HJ, Neuberg DS, Orav EJ, Colan SD. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol. 2010 Oct;11(10):950-61. doi: 10.1016/S1470-2045(10)70204-7. Epub 2010 Sep 16.
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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 (实际的)
2021年4月9日
初级完成 (预期的)
2021年10月1日
研究完成 (预期的)
2022年1月1日
研究注册日期
首次提交
2021年7月21日
首先提交符合 QC 标准的
2021年8月2日
首次发布 (实际的)
2021年8月9日
研究记录更新
最后更新发布 (实际的)
2021年8月9日
上次提交的符合 QC 标准的更新
2021年8月2日
最后验证
2021年8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.