Optimizing the Use of Morphine in Pre-Term Neonates

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2012 by Children's Research Institute
Sponsor:
Collaborators:
University of Louisville
State University of New York - Downstate Medical Center
Information provided by (Responsible Party):
Children's Research Institute
ClinicalTrials.gov Identifier:
NCT00494429
First received: June 28, 2007
Last updated: May 14, 2014
Last verified: April 2012
  Purpose

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


Condition Intervention Phase
Premature Neonates
Drug: Morphine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimizing Pain Treatment in Pre-Term Neonates

Resource links provided by NLM:


Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 60
Study Start Date: May 2005
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   22 Weeks to 32 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  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: NCT00494429

Contacts
Contact: Elaine Williams, RN, MSN 202-476-2245 efwillia@cnmc.org

Locations
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Elaine Williams, RN, MSN    202-476-2245      
Sponsors and Collaborators
Children's Research Institute
University of Louisville
State University of New York - Downstate Medical Center
Investigators
Principal Investigator: John N. van den Anker, M.D., Ph.D. Children's Research Institute
  More Information

No publications provided

Responsible Party: Children's Research Institute
ClinicalTrials.gov Identifier: NCT00494429     History of Changes
Other Study ID Numbers: PPRU-10750, Inulin IND #73093
Study First Received: June 28, 2007
Last Updated: May 14, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Research Institute:
Preterm Neonates
Morphine
Critically ill

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014