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.

Study Overview

• Status: Completed
• Conditions: Premature Neonates
• Intervention / Treatment: Drug: Morphine; Drug: Morphine

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 0.05 mg/kg I.V. morphine over 30-minutes, followed by a continuous infusion of 0.005 mg/kg/h.; Other Names: 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 Names: Inulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Infants will have continuous monitoring of vital signs, oxygen saturation, movements and adverse events to determine the safety of morphine.	study duration
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.	study duration
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.	study duration
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	study duration

Collaborators and Investigators

• Sponsor: John van den Anker
• Collaborators: Erasmus Medical Center; University of Louisville
• Investigators: Principal Investigator: John N. van den Anker, M.D., Ph.D., Children's National Research Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: June 28, 2007
• First Submitted That Met QC Criteria: June 28, 2007
• First Posted (Estimate): June 29, 2007

Study Record Updates

• Last Update Posted (Estimate): July 27, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Morphine; Critically ill; Preterm Neonates
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: PPRU-10750; Inulin IND #73093