Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Study Overview
=================
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.

Official Title
-----------------
Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Conditions
-----------------
Postoperative Pain in Infants

Intervention / Treatment
-----------------
* Drug: Ketorolac Tromethamine 1 mg/kg
* Drug: Ketorolac Tromethamine 0.5 mg/kg
* Drug: Placebo


Participation Criteria
=================
Eligibility 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)

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 18 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ketorolac 1 mg/kg<br>ketorolac 1 mg/kg iv given by 10 min infusion | Drug: Ketorolac Tromethamine 1 mg/kg<br>* 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.<br>* Other names: toradol;|
| Active Comparator: ketorolac 0.5 mg/kg<br>ketorolac 0.5 mg/kg iv given by 10 min infusion | Drug: Ketorolac Tromethamine 0.5 mg/kg<br>* 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.<br>* Other names: toradol;|
| Sham Comparator: placebo<br>placebo group received D5W 10 min infusion | Drug: Placebo<br>* 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.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ketorolac pharmacokinetics, ketorolac stereo-isomers, infants, postoperative analgesia, safety