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Morphine PK Subgroup Analysis

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ClinicalTrials.gov Identifier: NCT01322191
Recruitment Status : Completed
First Posted : March 24, 2011
Last Update Posted : October 29, 2012
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Tracking Information
First Submitted Date  ICMJE March 22, 2011
First Posted Date  ICMJE March 24, 2011
Last Update Posted Date October 29, 2012
Study Start Date  ICMJE April 2008
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2012)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2011)
Chemical analysis of the plasma and urine samples for morphine concentration using high performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2012)
  • Pharmacokinetic analysis of morphine, M3G, and M6G in urine to determine clearance and percent of dose excreted [ Time Frame: 2 hours ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2011)
  • Pharmacokinetic analysis of morphine, M3G, and M6G in urine to determine clearance and percent of dose excreted
  • Analgesic efficacy using drug concentration and area under the curve ratio correlated with the level of analgesia measured with the age-appropriate scale
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Morphine PK Subgroup Analysis
Official Title  ICMJE 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
Brief 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Post Operative Pain
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Drug: Morphine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2011)
48
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01322191
Other Study ID Numbers  ICMJE 10920
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert Ward, MD University of Utah
Principal Investigator: Mary Lieh-Lai, MD Children's Hospital of Michigan
PRS Account Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Verification Date March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP