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Optimizing the Use of Morphine in Pre-Term Neonates

This study has been completed.
Sponsor:
Collaborators:
University of Louisville
State University of New York - Downstate Medical Center
Information provided by (Responsible Party):
John van den Anker, Children's Research Institute
ClinicalTrials.gov Identifier:
NCT00494429
First received: June 28, 2007
Last updated: November 5, 2014
Last verified: November 2014

June 28, 2007
November 5, 2014
May 2005
November 2014   (final data collection date for primary outcome measure)
  • Safety: Infants will have continuous monitoring of vital signs, oxygen saturation, movements and adverse events to determine the safety of morphine. [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
  • Pharmacodynamics: The Neonatal Infant Pain (NIP) and Premature Infant Pain Profile (PIPP) will be performed at baseline, (prior to drug administration)and at pre-determined time intervals after the dose to assess pain for the efficacy of morphine. [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Pharmacokinetics: The concentrations of morphine and its metabolites will be measured in plasma and urine at pre-determined time points and will be used to calculate the formation and elimination clearances of morphine and its metabolites. [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Pharmacogenetics: Impact of genetic variation in the UGT2B7 gene on the formation clearances of the morphine metabolites will be studied as well as the genetic variation in the µ-opioid receptor, COMT, and β-arrestin 2 genes on the PD of morphine use [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Safety: Infants will have continuous monitoring of vital signs, oxygen saturation, movements and adverse events to determine the safety of morphine.
  • Pharmacodynamics: The Neonatal Infant Pain (NIP) and Premature Infant Pain Profile (PIPP) will be performed at baseline, (prior to drug administration)and at pre-determined time intervals after the dose to assess pain for the efficacy of morphine.
  • Pharmacokinetics: The concentrations of morphine and its metabolites will be measured in plasma and urine at pre-determined time points and will be used to calculate the formation and elimination clearances of morphine and its metabolites.
  • Pharmacogenetics: Impact of genetic variation in the UGT2B7 gene on the formation clearances of the morphine metabolites will be studied as well as the genetic variation in the µ-opioid receptor, COMT, and β-arrestin 2 genes on the PD of morphine use
Complete list of historical versions of study NCT00494429 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Optimizing the Use of Morphine in Pre-Term Neonates
Optimizing Pain Treatment in Pre-Term Neonates

The purpose of this study is to improve the dosing of morphine in critically ill premature neonates.

The investigators hypothesize that identifying co-variates predictive of variability in morphine disposition and/or response will provide the scientific basis for rationale and individualized morphine dosing schemes in neonates and young infants.

60 preterm neonates ranging in gestational age from 22 to 32 weeks will be recruited from the NICU. Stratification by gestational age will be done to ensure broad representation. The decision to initiate morphine therapy will be based solely on clinical indications. Prior to morphine dosing, a biochemical assessment of hepatic and renal function will be obtained. A 0.05 mg/kg loading dose of morphine will be given by an intravenous infusion over 30-minutes in preterm neonates with a gestational age of less than 29 weeks, followed by a continuous infusion of 0.005 mg/kg/h, whereas a loading dose of 0.1 mg/kg will be given in preterm neonates with a gestational age of 29 weeks or more followed by a continuous infusion of 0.01 mg/kg/h. Pain assessment will be performed at baseline (prior to study medication administration) and at .5, 1, 2, 4, 8, 12 and 24 hours after the dose. At each of these time points infants will be videotaped for two minutes with two cameras. Videotapes will be scored afterward using standard validated pain assessment tools for preterm infants.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Premature Neonates
  • Drug: Morphine
    Gestational Age< 29 weeks: A loading dose of 0.05 mg/kg I.V. morphine over 30-minutes, followed by a continuous infusion of 0.005 mg/kg/h.
    Other Name: inulin
  • Drug: Morphine
    Gestational Age>= 29 weeks: A loading dose of 0.1 mg/kg I.V. morphine over 30-minutes, followed by a continuous infusion of 0.01 mg/kg/h.
    Other Name: Inulin
  • Experimental: 1
    Gestational Age< 29 weeks will be administered a loading dose of 0.05 mg/kg I.V. morphine over 30-minutes, followed by a continuous infusion of 0.005 mg/kg/hr.
    Intervention: Drug: Morphine
  • Experimental: 2
    Gestational Age>= 29 weeks will be administered a loading dose of 0.1 mg/kg I.V. morphine over 30-minutes, followed by a continuous infusion of 0.01 mg/kg/h.
    Intervention: Drug: Morphine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
November 2014
November 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Preterm neonates of both genders and all races
  • postnatal age less than 30 days
  • an indwelling (peripheral or umbilical) arterial line, and
  • a clinical indication for intravenous morphine administration

Exclusion Criteria:

  • Neonates with severe asphyxia, grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations, neurological disorders, and those receiving continuous or intermittent neuromuscular blockers.
  • clinical or biochemical evidence of hepatic and renal compromise (including systemic hypoperfusion) or
  • received drugs that are UGT2B7 substrates (including Lorazepam, ibuprofen, valproic acid, naloxone and other morphine derivatives or propanolol)
Both
22 Weeks to 32 Weeks
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00494429
PPRU-10750, Inulin IND #73093
No
John van den Anker, Children's Research Institute
John van den Anker
  • University of Louisville
  • State University of New York - Downstate Medical Center
Principal Investigator: John N. van den Anker, M.D., Ph.D. Children's Research Institute
Children's Research Institute
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP