Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Infants handle ketorolac differently than adults. Study of handling of this pain medication given to infants following surgery. Detailed analysis of how the drug is eliminated from age 2 months to 18 months. Compared morphine use in infants who received the drug to the group getting placebo. Safety testing for kidney and liver function, breathing measured by continuous oximetry, and any bleeding issues.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain in Infants
• Intervention / Treatment: Drug: Ketorolac Tromethamine 1 mg/kg; Drug: Ketorolac Tromethamine 0.5 mg/kg; Drug: Placebo

Detailed Description

Population kinetic analysis of ketorolac stereo-isomer concentrations after single dose given postoperatively in infants aged 2-18 months. Safety assessments of renal and hepatic function tests by blood tests before and after drug administration, urinalysis pre- and post-drug, continuous oximetry before and for 12 hours after drug. Morphine use between active drug groups and placebo group in the first 24 hours after surgery was assessed as a surrogate analgesic measure in these non-verbal infants. A modified infant pain scale was used to assure consistent pain management.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-prematurely-born infants admitted to hospital following surgery ages 2-18 months, studied by age group 12-18 months, 6-12 months, < 6 months

Exclusion Criteria:

• Bleeding history in infant or family
• Coagulopathy
• Gastrointestinal bleeding history
• Renal or hepatic disease assessed by history and by pre-drug blood tests
• Premature birth (<36 weeks gestation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ketorolac 1 mg/kg; ketorolac 1 mg/kg iv given by 10 min infusion	Drug: Ketorolac Tromethamine 1 mg/kg; Ketorolac Tromethamine 1 mg/kg infusion over 10 minutes intravenous (IV) infusion. Blood sampling in for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.; Other Names: toradol
Active Comparator: ketorolac 0.5 mg/kg; ketorolac 0.5 mg/kg iv given by 10 min infusion	Drug: Ketorolac Tromethamine 0.5 mg/kg; Ketorolac Tromethamine 0.5 mg/kg infusion over 10 minutes intravenous (IV) infusion. Blood sampling for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.; Other Names: toradol
Sham Comparator: placebo; placebo group received D5W 10 min infusion	Drug: Placebo; Dextrose in water (D5W) infusion over 10 minutes intravenous (IV) infusion. Blood sampling for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.; Other Names: Dextrose in water (D5W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery	stereo-isomer specific clearance determined by population-based pharmacokinetic analysis (NONMEM)	24 hours following surgery
Central Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants	stereo-specific ketorolac analysis using population-based analysis (NONMEM)for ketorolac given intravenously 24 hours after surgery in 2-6 month old infants	24 hours after surgery
Peripheral Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants	peripheral volume of distribution for ketorolac stereo-isomers determined by population kinetic analysis (NONMEM)	24 hours post surgery
Half-life of S- and R+ Ketorolac in 2-6 Month Old Infants	half-life calculated from non-compartmental analysis of ketorolac isomers in 2-6 month old infants given intravenous ketorolac following surgery	24 hours after surgery
Clearance of S- and R+ Ketorolac in 6-18 Month Old Infants	stereo-specific ketorolac clearance by population-based analysis (NONMEM)	24 hours after surgery
Volume of Distribution for Ketorolac Isomers in 6-18 Month Old Infants	population-based kinetic analysis of ketorolac isomers following intravenous infusion in infants after surgery	24 hours after surgery
Ketorolac Stereo-isomer Volume of Distribution Peripheral in 6-18 Month Old Infants	population-based analysis of ketorolac stereo-isomers	24 hours after surgery
Half-life of Ketorolac Stereo-isomers in 6-18 Month Old Infants After Surgery	noncompartmental pharmacokinetic analysis of ketorolac stereo-isomers after intravenous infusion in postoperative infants	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Use in 2-6 Month Old Infants Given Ketorolac or Placebo Following Surgery	total morphine given intravenously in the 12 hours following receiving intravenous ketorolac or placebo	first day after surgery
Percent Time With Room Air Oximetry Saturations Under 90% in 2-6 Month Infants	continuous oximetry monitoring of room air saturation was collected for 12 hours after intravenous infusion of ketorolac or placebo	12 hours after ketorolac or placebo infusion
Total Morphine Use in 6-18 Month Old Infants After Ketorolac or Placebo Intravenous Infusion After Surgery	total amount of morphine given for 12 hours after ketorolac or placebo infusion in 6-18 month old infants after surgery	24 hours after surgery
Oximetry Saturation Under 90% After Ketorolac or Placebo Infusion in 6-18 Month Old Infants	continuous oximetry monitoring for 12 hours after ketorolac or placebo intravenous infusion in 6-18 month old infants after surgery	24 hours after surgery

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Collaborators: University of Washington
• Investigators: Principal Investigator: Anne M. Lynn, MD, Seattle Children's Hospital

Publications and helpful links

General Publications

• Lynn AM, Bradford H, Kantor ED, Seng KY, Salinger DH, Chen J, Ellenbogen RG, Vicini P, Anderson GD. Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anesth Analg. 2007 May;104(5):1040-51, tables of contents. doi: 10.1213/01.ane.0000260320.60867.6c.
• Lynn AM, Bradford H, Kantor ED, Andrew M, Vicini P, Anderson GD. Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months. Paediatr Anaesth. 2011 Mar;21(3):325-34. doi: 10.1111/j.1460-9592.2010.03484.x. Epub 2010 Dec 29.

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 14, 2010
• First Posted (Estimate): December 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 13, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: safety; infants; postoperative analgesia; ketorolac pharmacokinetics; ketorolac stereo-isomers
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: IND 59883