Optimizing the Use of Morphine in Pre-Term Neonates - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators:	Children's Hospital of Louisville Emory University
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00494429

Purpose

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

Condition	Intervention	Phase
Critically Ill Premature Neonates	Drug: Morphine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Optimizing Pain Treatment in Pre-Term Neonates

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

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 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Gestational Age< 29 weeks	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.
2: Experimental Gestational Age>= 29 weeks	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.

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

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

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Children's Hospital of Louisville

Emory University

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 National Medical Center ( John van den Anker, MD, PhD/Principal Investigator )
Study ID Numbers:	PPRU-10750, Inulin IND #73093
Study First Received:	June 28, 2007
Last Updated:	May 19, 2009
ClinicalTrials.gov Identifier:	NCT00494429 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Preterm Neonates, Morphine, critically ill

Additional relevant MeSH terms:

Morphine
Disease Attributes
Physiological Effects of Drugs
Central Nervous System Depressants
Narcotics
Pharmacologic Actions
Pathologic Processes

Critical Illness
Sensory System Agents
Therapeutic Uses
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on February 08, 2010