Hypothermia's Impact on Pharmacology

Cardiac Arrest Clinical Trial

— HIP  

Official title:

Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01560338
• Other study ID #: 12-009214
• Secondary ID: RO1HL11274501A1
• Status: Completed
• Start date: March 2012
• Est. completion date: January 28, 2018

Study information

• Verified date: March 2021
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the study will help us understand the complex interaction between hypothermia (cooling) and pharmacogenetics (how specific genes effect how drugs are handled), and their impact on how routinely given sedation drug are broken down and used by the body when given to children after cardiac arrest (when heart stops pumping blood) and are critically ill.

Description:

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

1. To estimate the impact of hypothermia on the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest and

2. 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 28, 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Hypothermia

Locations

Country	Name	City	State
United States	Univeristy of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Nationwide Children's Medical Center	Columbus	Ohio
United States	Pennsylvania State University Hersey Medical Center	Hershey	Pennsylvania
United States	University of Louisville	Louisville	Kentucky
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Manifestations of hypothermia	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.	2.5 years
Primary	Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam	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.	2.5 years
Secondary	Impact of genetic factors	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.	2.5 years