Morphine PK Subgroup Analysis

Post Operative Pain Clinical Trial

Official title: A Randomized Controlled Comparison of Ketorolac Tromethamine and Morphine for Postoperative Analgesia in Critically-ill, 3-18 Year-old Children: A Subgroup Analysis of Developmental Changes in Morphine Kinetics and Efficacy

Status Completed

Clinical Trial Summary

This study was originally undertaken to evaluate the analgesic efficacy of an intravenously administered dose of ketorolac compared with intravenous morphine in the relief of acute, postoperative pain in children admitted to the Intensive Care Unit. Using the urine and plasma samples originally collected from patients in the morphine treatment group and which were never analyzed, this proposal seeks to study the pharmacokinetics and metabolism of intravenous morphine in critically-ill children along with its concentration-related efficacy using prior measures of pain.

Clinical Trial Description

This was a randomized, double-blind, parallel, single-dose study. All children admitted to the ICU at Children's Hospital of Michigan postoperatively who required pain management were candidates. Enrollment required a Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and/or Oucher pain score meeting the protocol definition of moderate to severe pain. Each patient was randomly assigned to receive a single dose of either morphine 0.1 mg/kg or ketorolac 0.6 mg/kg IV as the first postoperative analgesic after arriving in the ICU. Two-milliliter venous blood samples were drawn from a site contralateral to the infusion site. Samples were obtained before the dose and at 15, 30, and 60 minutes, hourly from 1-6 hours, and at 8 and 12 hours timed from the beginning of the infusion. Pain scales were assessed at the time of each pharmacokinetic sample. Plasma was immediately separated and frozen at -80°C. Urine was quantitatively collected for 12-24 hours after the study drug was administered. Urine was kept on ice at 3°C throughout the collection. At completion of the collection, the urine volume was measured and recorded, and an aliquot was frozen and maintained at -80°C. The plasma and urine samples from the morphine treated group in the original study were stored at -80°C and were not analyzed. Sets of samples of urine and plasma from 6 subjects over a range of ages have been analyzed to insure that the samples have not deteriorated during storage. This subanalysis study will provide chemical analysis of the plasma and urine samples for morphine, morphine 3 glucuronide (M3G) and morphine 6 glucuronide (M6G); pharmacokinetic analysis of morphine and its metabolites with comparison to demographics; and comparison of the morphine concentrations to the measures of analgesia. The ratio of the area under the plasma concentration vs time curves (AUC)of M6G with twice the analgesic potency as morphine and M3G with theoretical anti-analgesic properties will be compared to analgesic effects measured by the age-appropriate pain scales. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Pain, Postoperative
• Post Operative Pain

• NCT number: NCT01322191
• Study type: Interventional
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Status: Completed
• Phase: Phase 4
• Start date: April 2008
• Completion date: November 2010