Optimizing the Use of Morphine in Pre-Term Neonates

Premature Neonates Clinical Trial

Official title:

Optimizing Pain Treatment in Pre-Term Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00494429
• Other study ID #: PPRU-10750
• Secondary ID: Inulin IND #7309
• Status: Completed
• Phase: Phase 2
• First received: June 28, 2007
• Last updated: July 25, 2016
• Start date: May 2005
• Est. completion date: November 2015

Study information

• Verified date: July 2016
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Weeks to 32 Weeks

Eligibility

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)

Related Conditions & MeSH terms

• Premature Birth
• Premature Neonates

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
John van den Anker	Erasmus Medical Center, University of Louisville

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Infants will have continuous monitoring of vital signs, oxygen saturation, movements and adverse events to determine the safety of morphine.		study duration
Primary	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
Primary	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
Primary	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 ß-arrestin 2 genes on the PD of morphine use		study duration