Hypothermia's Impact on Pharmacology (HIP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01560338
First received: March 20, 2012
Last updated: March 4, 2015
Last verified: February 2015
  Purpose

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.


Condition
Cardiac Arrest
Hypothermia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Impact of genetic factors [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Manifestations of hypothermia [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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

Whole blood


Enrollment: 31
Study Start Date: March 2012
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pediatric Cardiac Arrest
Pediatric patients age greater than 48 hours (with corrected gestational age of at least 38 weeks) and less than 18 years suffering cardiac arrest for at least 2 minutes.

Detailed 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. The parent trial, "Therapeutic Hypothermia After Pediatric Cardiac Arrest", comparing the efficacy of therapeutic normothermia vs. hypothermia to improve neurologic survival, provides a unique opportunity to study the impact of organ failure, pharmacogenetics and hypothermia on metabolism, clearance and drug disposition. 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 ancillary study, Hypothermia's Impact on Pharmacology, are:

  1. To identify the physiologic manifestations of cardiac arrest and MODS that underlie the variability in morphine and midazolam pharmacokinetics;
  2. To estimate the impact of genetic factors on the variability in morphine and midazolam pharmacokinetics, specifically in the setting of pediatric cardiac arrest and
  3. To estimate the impact of hypothermia on the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest.

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

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The study population is the pediatric population greater than 48 hours (with a corrected gestational age of at least 38 weeks) and less than 18 years of age who are enrolled in the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Clinical Trial AND have had or having morphine and/or midazolam administered as part of clinical care.

Criteria

Inclusion Criteria:

  • Enrolled in Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Clinical Trial
  • Be greater than or equal to three (3) kg
  • Receiving or have received morphine and/or midazolam as part of clinical care
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01560338

  Show 19 Study Locations
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Athena F Zuppa, MD MSCE Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01560338     History of Changes
Other Study ID Numbers: 12-009214, RO1HL11274501A1
Study First Received: March 20, 2012
Last Updated: March 4, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Pharmacokinetics
Midazolam
Morphine
Cardiac Arrest
Hypothermia

Additional relevant MeSH terms:
Heart Arrest
Hypothermia
Body Temperature Changes
Cardiovascular Diseases
Heart Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on July 05, 2015