Hypothermia's Impact on Pharmacology (HIP)
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|ClinicalTrials.gov Identifier: NCT01560338|
Recruitment Status : Completed
First Posted : March 22, 2012
Last Update Posted : April 11, 2018
|Condition or disease|
|Cardiac Arrest Hypothermia|
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.
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.
Prospective pharmacokinetic study
|Study Type :||Observational|
|Actual Enrollment :||41 participants|
|Official Title:||Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics|
|Actual Study Start Date :||March 2012|
|Actual Primary Completion Date :||January 2018|
|Actual Study Completion Date :||January 28, 2018|
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.
- Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam [ Time Frame: 2.5 years ]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.
- Impact of genetic factors [ Time Frame: 2.5 years ]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.
- Manifestations of hypothermia [ Time Frame: 2.5 years ]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.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01560338
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Kentucky|
|University of Louisville|
|Louisville, Kentucky, United States, 40202|
|United States, Michigan|
|Univeristy of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Ohio|
|Nationwide Children's Medical Center|
|Columbus, Ohio, United States, 43205|
|United States, Pennsylvania|
|Pennsylvania State University Hersey Medical Center|
|Hershey, Pennsylvania, United States, 19104|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Principal Investigator:||Athena F Zuppa, MD MSCE||Children's Hospital of Philadelphia|