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Hypothermia's Impact on Pharmacology (HIP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01560338
First received: March 20, 2012
Last updated: August 1, 2016
Last verified: August 2016
  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

Estimated Enrollment: 41
Study Start Date: March 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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. 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

  Eligibility

Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population is the pediatric population equal to or greater than 3 kg and less than 18 years of age AND have had or currently receiving morphine and/or midazolam AND receive hypothermia after cardiac arrest administered as part of clinical care.
Criteria

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
  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

Contacts
Contact: Athena Zuppa, MD MSCE 267-426-7359 zuppa@email.chop.edu
Contact: Janice L Prodell, RN CCRC 215-590-4924 prodell@chop.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Crystal Hock, RN BSN    205-996-3313    khock@peds.uab.edu   
Principal Investigator: Jeffery A Alten, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Elyse Tomanio, RN    202-476-3389    etomanio@cnmc.org   
Principal Investigator: John T Berger III, MD         
United States, Kentucky
University of Louisville Completed
Louisville, Kentucky, United States, 40202
United States, Michigan
Univeristy of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Frank Moler, MD    734-764-5302    fmoler@med.umich.edu   
Contact: Nicholas Harris    (734) 763.7131    harrisnl@med.umich.edu   
Principal Investigator: Frank Moler, MD         
United States, Ohio
Nationwide Children's Medical Center Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Lisa Steele, RN CCRN    614-355-3504    lisa.steele@nationwidechildrens.org   
Principal Investigator: Andrew R Yates, MD         
United States, Pennsylvania
Pennsylvania State University Hersey Medical Center Recruiting
Hersey, Pennsylvania, United States, 19104
Contact: Debbie Spear, RN CCRN    717-531-5193    dsspeat@hmc.pcu.edu   
Principal Investigator: Neal Thomas, MD, MSc         
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Athena Zuppa, MD MSCE    267-426-7359    zuppa@email.chop.edu   
Contact: Janice L Prodell, RN CCRC    (215) 590.4924    prodell@chop.edu   
Principal Investigator: Athena F Zuppa, MD MSCE         
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Alan C Abraham    412-692-7626    abraac@UPMC.edu   
Principal Investigator: Joseph A Carcillo Jr, MD         
United States, Washington
Seattle Children't Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Erin Sullivan, MPH    206-987-4558    erin.sullivan@seattlechildrens.org   
Principal Investigator: Jerry Zimmerman, MD PhD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Athena F Zuppa, MD MSCE Children's Hospital of Philadelphia
  More Information

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: August 1, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
Heart Arrest
Hypothermia
Heart Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Morphine
Midazolam
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016