Morphine PK Subgroup Analysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01322191
First received: March 22, 2011
Last updated: October 26, 2012
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Post Operative Pain
Drug: Morphine
Phase 4

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Chemical analysis of the plasma and urine samples for morphine concentration using high performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic analysis of morphine, M3G, and M6G in urine to determine clearance and percent of dose excreted [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  • Analgesic efficacy using drug concentration and area under the curve ratio correlated with the level of analgesia measured with the age-appropriate scale [ Time Frame: 6 months to 1 year ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: April 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Random assignment to a single dose of morphine 0.1 mg/kg infused by syringe pump over 10 minutes; urine and blood sample frozen at -80 degrees Celsius
Drug: Morphine
A single dose of morphine 0.1 mg/kg infused by syringe pump over 10 minutes; urine and blood sample frozen at -80 degrees Celsius

Detailed 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.

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All children 3-18 years of age admitted to the ICU at Children's Hospital of Michigan postoperatively who required pain management during the immediate postoperative period
  • Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and/or Oucher pain score meeting the protocol definition of moderate to severe pain

Exclusion Criteria:

  • Coma (Glasgow Coma Score < 8) or significant post-operative sedation that prevented the patient from appropriate responses to questions
  • Requirement of administration of a sedative or neuromuscular blocking agent, or intrathecal narcotics immediately after surgery
  • Gastrointestinal hemorrhage and/or history of ulcer disease
  • Frequent use of NSAIDs or narcotic analgesics for >2 weeks within the 1-month period before the study
  • Asthma
  • Known hypersensitivity to NSAIDs, aspirin or opiates
  • Nephrotic syndrome or acute/chronic renal failure
  • Thrombocytopenia (platelet count <100,000)
  • Congestive heart failure
  • Hepatic failure
  • Treatment with methotrexate, thiazides, β-blocking agents or warfarin at the time of the study
  • Dehydration or hypovolemia
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01322191

Locations
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Ward, MD University of Utah
Principal Investigator: Mary Lieh-Lai, MD Children's Hospital of Michigan
  More Information

No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01322191     History of Changes
Other Study ID Numbers: 10920
Study First Received: March 22, 2011
Last Updated: October 26, 2012
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
pain, pain management, pediatrics, morphine pharmacokinetics

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Morphine
Ketorolac Tromethamine
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
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014