Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
研究概览
详细说明
Background:
Therapeutic hypothermia is used in the pediatric intensive care unit, and is being studied in the setting of pediatric cardiac arrest. Following cardiac arrest, multiple organ dysfunction syndrome, especially renal and hepatic dysfunction, is common and affects the metabolism and excretion of drugs. In addition, very little is known about the impact of hypothermia on a child's ability to metabolize medications. Dose adjustments may be required in the setting of hypothermia to avoid under-dosing and over-dosing of medications. Improper dosing and drug accumulation of sedatives and opiates can worsen existing neurologic, circulatory and respiratory failure. The measurement of the actual drug and metabolite concentrations in the body (pharmacokinetics) provides information on how a child metabolizes medications. In addition, variability in these concentrations after the administration of equal doses to different children may result from genetically driven differences in drug metabolizing systems (pharmacogenetics). Finally, these genetic differences may respond differently to hypothermia. Our overarching hypothesis is that morphine and midazolam disposition will be affected by temperature management even when accounting for potentially confounding quantifiable factors of organ dysfunction and genetic differences.
Objectives:
The objectives of this study, Hypothermia's Impact on Pharmacology 2, are
- To estimate the impact of hypothermia on the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest and
- To estimate the impact of genetic factors on the variability in morphine and midazolam pharmacokinetics, specifically in the setting of hypothermia.
Sophisticated modeling and simulation techniques will be utilized to examine the highly dynamic changes in physiology associated with critical illness, drug disposition, pharmacogenetics and temperature modulation. The models created using this approach will be implemented to optimize the prospective treatment of these critically ill children.
Study Design:
Prospective pharmacokinetic study
研究类型
注册 (实际的)
联系人和位置
学习地点
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Alabama
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Birmingham、Alabama、美国、35294
- University of Alabama at Birmingham
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District of Columbia
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Washington、District of Columbia、美国、20010
- Children's National Medical Center
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Kentucky
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Louisville、Kentucky、美国、40202
- University of Louisville
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Michigan
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Ann Arbor、Michigan、美国、48109
- Univeristy of Michigan
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Ohio
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Columbus、Ohio、美国、43205
- Nationwide Children's Medical Center
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Pennsylvania
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Hershey、Pennsylvania、美国、19104
- Pennsylvania State University Hersey Medical Center
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Philadelphia、Pennsylvania、美国、19104
- The Children'S Hospital Of Philadelphia
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Pittsburgh、Pennsylvania、美国、15224
- University of Pittsburgh
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Washington
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Seattle、Washington、美国、98105
- Seattle Children's Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Be greater than or equal to three (3) kg
- Receiving or have received morphine and/or midazolam as part of clinical care
- Receiving hypothermia after any cardiac arrest
- Provide Informed Consent
Exclusion Criteria:
- Receiving renal replacement therapy [example Continuous Veno-Venous Hemofiltration (CVVH), Continuous Veno-Venous Hemodialysis (CVVHD), and Continuous Veno-Venous Hemodiafiltration (CVVHDF)]
- Receiving plasmapheresis
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Pediatric after Cardiac Arrest
Pediatric patients greater than 3 kg.
and less than 18 years suffering cardiac arrest who have been given or currently receiving morphine and/or midazolam and receiving hypothermia.
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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 |
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Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
大体时间:2.5 years
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The objective of this aim is to identify the physiologic manifestations of cardiac arrest and MODS that underlie the variability in morphine and midazolam pharmacokinetics.
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2.5 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Impact of genetic factors
大体时间:2.5 years
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The objective of this aim is to estimate the impact of genetic factors that underlie the variability in morphine and midazolam pharmacokinetics (PK), specifically in the setting of pediatric cardiac arrest.
In this aim we will investigate the effect of genotype on pharmacokinetic parameters for morphine and midazolam.
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2.5 years
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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Manifestations of hypothermia
大体时间:2.5 years
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The objective of this aim is to identify the manifestations of hypothermia that underlie the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest.
In this aim we will investigate the effect of body temperature on PK parameters for morphine and midazolam.
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2.5 years
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合作者和调查者
调查人员
- 首席研究员:Athena F Zuppa, MD MSCE、Children's Hospital of Philadelphia
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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