Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Phase 3

Completed

Conditions: Postoperative Pain in Infants

Interventions: Drug: Ketorolac Tromethamine 1 mg/kg
Drug: Ketorolac Tromethamine 0.5 mg/kg
Drug: Placebo

Registration Number: NCT01260883

Lead Sponsor: Seattle Children's Hospital

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ketorolac 1 mg/kg	Ketorolac Tromethamine 1 mg/kg	ketorolac 1 mg/kg iv given by 10 min infusion
ketorolac 0.5 mg/kg	Ketorolac Tromethamine 0.5 mg/kg	ketorolac 0.5 mg/kg iv given by 10 min infusion
placebo	Placebo	placebo group received D5W 10 min infusion

Primary Outcome Measures

Name	Time	Method
Volume of Distribution for Ketorolac Isomers in 6-18 Month Old Infants	24 hours after surgery	population-based kinetic analysis of ketorolac isomers following intravenous infusion in infants after surgery
Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery	24 hours following surgery	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	24 hours after surgery	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	24 hours post surgery	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	24 hours after surgery	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	24 hours after surgery	stereo-specific ketorolac clearance by population-based analysis (NONMEM)
Ketorolac Stereo-isomer Volume of Distribution Peripheral in 6-18 Month Old Infants	24 hours after surgery	population-based analysis of ketorolac stereo-isomers
Half-life of Ketorolac Stereo-isomers in 6-18 Month Old Infants After Surgery	24 hours after surgery	noncompartmental pharmacokinetic analysis of ketorolac stereo-isomers after intravenous infusion in postoperative infants

Secondary Outcome Measures

Name	Time	Method
Morphine Use in 2-6 Month Old Infants Given Ketorolac or Placebo Following Surgery	first day after surgery	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	12 hours after ketorolac or placebo infusion	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	24 hours after surgery	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	24 hours after surgery	continuous oximetry monitoring for 12 hours after ketorolac or placebo intravenous infusion in 6-18 month old infants after surgery