Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
調査の概要
詳細な説明
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
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Alabama
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Birmingham、Alabama、アメリカ、35294
- University of Alabama at Birmingham
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District of Columbia
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Washington、District of Columbia、アメリカ、20010
- Children's National Medical Center
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Kentucky
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Louisville、Kentucky、アメリカ、40202
- University of Louisville
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- Univeristy of Michigan
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Ohio
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Columbus、Ohio、アメリカ、43205
- Nationwide Children's Medical Center
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Pennsylvania
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Hershey、Pennsylvania、アメリカ、19104
- Pennsylvania State University Hersey Medical Center
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Philadelphia、Pennsylvania、アメリカ、19104
- The Children's Hospital of Philadelphia
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Pittsburgh、Pennsylvania、アメリカ、15224
- University of Pittsburgh
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Washington
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Seattle、Washington、アメリカ、98105
- Seattle Children's Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
コホートと介入
グループ/コホート |
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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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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Impact of genetic factors
時間枠: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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Manifestations of hypothermia
時間枠: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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協力者と研究者
捜査官
- 主任研究者:Athena F Zuppa, MD MSCE、Children's Hospital of Philadelphia
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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