Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

This study has been completed.
Sponsor:
Collaborator:
University of Washington
Information provided by (Responsible Party):
Anne M. Lynn, Seattle Children's Hospital
ClinicalTrials.gov Identifier:
NCT01260883
First received: December 9, 2010
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Postoperative Pain in Infants
Drug: Ketorolac Tromethamine 1 mg/kg
Drug: Ketorolac Tromethamine 0.5 mg/kg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Resource links provided by NLM:


Further study details as provided by Seattle Children's Hospital:

Primary Outcome Measures:
  • Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery [ Time Frame: 24 hours following surgery ] [ Designated as safety issue: No ]
    stereo-isomer specific clearance determined by population-based pharmacokinetic analysis (NONMEM)

  • Central Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    stereo-specific ketorolac analysis using population-based analysis (NONMEM)for ketorolac given intravenously 24 hours after surgery in 2-6 month old infants

  • Peripheral Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants [ Time Frame: 24 hours post surgery ] [ Designated as safety issue: No ]
    peripheral volume of distribution for ketorolac stereo-isomers determined by population kinetic analysis (NONMEM)

  • Half-life of S- and R+ Ketorolac in 2-6 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    half-life calculated from non-compartmental analysis of ketorolac isomers in 2-6 month old infants given intravenous ketorolac following surgery

  • Clearance of S- and R+ Ketorolac in 6-18 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    stereo-specific ketorolac clearance by population-based analysis (NONMEM)

  • Volume of Distribution for Ketorolac Isomers in 6-18 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    population-based kinetic analysis of ketorolac isomers following intravenous infusion in infants after surgery

  • Ketorolac Stereo-isomer Volume of Distribution Peripheral in 6-18 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    population-based analysis of ketorolac stereo-isomers

  • Half-life of Ketorolac Stereo-isomers in 6-18 Month Old Infants After Surgery [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    noncompartmental pharmacokinetic analysis of ketorolac stereo-isomers after intravenous infusion in postoperative infants


Secondary Outcome Measures:
  • Morphine Use in 2-6 Month Old Infants Given Ketorolac or Placebo Following Surgery [ Time Frame: first day after surgery ] [ Designated as safety issue: No ]
    total morphine given intravenously in the 12 hours following receiving intravenous ketorolac or placebo

  • Percent Time With Room Air Oximetry Saturations Under 90% in 2-6 Month Infants [ Time Frame: 12 hours after ketorolac or placebo infusion ] [ Designated as safety issue: Yes ]
    continuous oximetry monitoring of room air saturation was collected for 12 hours after intravenous infusion of ketorolac or placebo

  • Total Morphine Use in 6-18 Month Old Infants After Ketorolac or Placebo Intravenous Infusion After Surgery [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    total amount of morphine given for 12 hours after ketorolac or placebo infusion in 6-18 month old infants after surgery

  • Oximetry Saturation Under 90% After Ketorolac or Placebo Infusion in 6-18 Month Old Infants [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: Yes ]
    continuous oximetry monitoring for 12 hours after ketorolac or placebo intravenous infusion in 6-18 month old infants after surgery


Enrollment: 77
Study Start Date: May 2000
Study Completion Date: December 2010
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Dextrose in water (D5W)

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.

  Eligibility

Ages Eligible for Study:   2 Months to 18 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01260883

Locations
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Seattle Children's Hospital
University of Washington
Investigators
Principal Investigator: Anne M. Lynn, MD Seattle Children's Hospital
  More Information

Publications:
Responsible Party: Anne M. Lynn, Professor, Anesthesiology and Pediatrics, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT01260883     History of Changes
Obsolete Identifiers: NCT00014716
Other Study ID Numbers: IND 59883
Study First Received: December 9, 2010
Results First Received: July 20, 2011
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Seattle Children's Hospital:
ketorolac pharmacokinetics
ketorolac stereo-isomers
infants
postoperative analgesia
safety

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Ketorolac Tromethamine
Ketorolac
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 20, 2014