Postoperative Pain in InfantsPhase 3NCT01260883

Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

A Phase 3 study testing Ketorolac Tromethamine 1 mg/kg and Ketorolac Tromethamine 0.5 mg/kg in people with Postoperative Pain in Infants, run by Seattle Children's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 2 to 18 months
Conditions the study is for: Postoperative Pain in Infants
What is being tested?: Ketorolac Tromethamine 1 mg/kg and Ketorolac Tromethamine 0.5 mg/kg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 77 participants
Where: 1 siteUnited States
Study dates: May 2000to Dec 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 18 months
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Seattle Children's Hospital
Seattle, Washington, 98105

Other trials in United States

About this study

Read the 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.

Conditions: Postoperative Pain in Infants
Being tested: Ketorolac Tromethamine 1 mg/kg, Ketorolac Tromethamine 0.5 mg/kg, Placebo
Keywords: ketorolac pharmacokinetics, ketorolac stereo-isomers, infants, postoperative analgesia, safety

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ketorolac Tromethamine 1 mg/kgDrug
Also called toradol
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.
Ketorolac Tromethamine 0.5 mg/kgDrug
Also called toradol
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.
PlaceboDrug
Also called Dextrose in water (D5W)
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.

Study groups in NCT01260883
Study group	Role	What they receive
ketorolac 1 mg/kg	Experimental	ketorolac 1 mg/kg iv given by 10 min infusion Receives: Drug: Ketorolac Tromethamine 1 mg/kg
ketorolac 0.5 mg/kg	Active comparator	ketorolac 0.5 mg/kg iv given by 10 min infusion Receives: Drug: Ketorolac Tromethamine 0.5 mg/kg
placebo	Sham comparator	placebo group received D5W 10 min infusion Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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
Measured: 24 hours after surgery
Ketorolac Stereo-isomer Volume of Distribution Peripheral in 6-18 Month Old Infants
population-based analysis of ketorolac stereo-isomers
Measured: 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
Measured: 24 hours after surgery

Secondary outcomes (4)

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
Measured: 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
Measured: 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
Measured: 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
Measured: 24 hours after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2000Dec 2010

First posted15 Dec 2010 (estimated)
Study startMay 2000
Primary completionMar 2008
Study completionDec 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Postoperative Pain in InfantsStudies of the same condition, open and under way.
More trials run by Seattle Children's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Care provider, Investigator
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01260883
Sponsor's protocol ID: IND 59883
Status last verified: Jun 2013
First submitted: 9 Dec 2010
Last updated: 13 Jun 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 17456651
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.
PubMed 21199130

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Ketorolac in Postoperative Infants: Pharmacokinetics and Safety
ClinicalTrials.gov ID: NCT01260883
Acronym / sponsor ID: IND 59883
Conditions: Postoperative Pain in Infants
Keywords: ketorolac pharmacokinetics, ketorolac stereo-isomers, infants, postoperative analgesia, safety
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: Seattle Children's HospitalUniversity, hospital or other
Collaborators: University of Washington
Study start: May 2000
Primary completion: Mar 2008 (actual)
Study completion: Dec 2010 (actual)
First posted: 15 Dec 2010 (estimated)
Results: Posted 8 Aug 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (care provider, investigator)
Number of arms: 3

Arm	Type	Receives
ketorolac 1 mg/kg	Experimental	Drug: Ketorolac Tromethamine 1 mg/kgketorolac 1 mg/kg iv given by 10 min infusion
ketorolac 0.5 mg/kg	Active comparator	Drug: Ketorolac Tromethamine 0.5 mg/kgketorolac 0.5 mg/kg iv given by 10 min infusion
placebo	Sham comparator	Drug: Placeboplacebo group received D5W 10 min infusion

Who may qualify

Ages: 2 to 18 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (1 listed)

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

Key exclusion criteria (5 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ketorolac Tromethamine 1 mg/kgAlso: toradolKetorolac 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.	Drug	ketorolac 1 mg/kg
Ketorolac Tromethamine 0.5 mg/kgAlso: toradolKetorolac 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.	Drug	ketorolac 0.5 mg/kg
PlaceboAlso: Dextrose in water (D5W)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.	Drug	placebo

Primary outcome

Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 24 hours after surgery
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
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
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
noncompartmental pharmacokinetic analysis of ketorolac stereo-isomers after intravenous infusion in postoperative infants

4 secondary outcomes

Morphine Use in 2-6 Month Old Infants Given Ketorolac or Placebo Following Surgery
Time frame: first day after surgery
Percent Time With Room Air Oximetry Saturations Under 90% in 2-6 Month Infants
Time frame: 12 hours after ketorolac or placebo infusion
Total Morphine Use in 6-18 Month Old Infants After Ketorolac or Placebo Intravenous Infusion After Surgery
Time frame: 24 hours after surgery
Oximetry Saturation Under 90% After Ketorolac or Placebo Infusion in 6-18 Month Old Infants
Time frame: 24 hours after surgery

Results and safety

Results posted to the registry on 8 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketorolac 1 mg/kg Intravenous	22	22
Ketorolac 0.5 mg/kg Intravenous	11	11
Dextrose 5% in Water (D5W)	18	18

Primary outcome: Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery

Time frame: 24 hours following surgery. Mean (Standard Error). Unit: ml/min

Measure	S- Ketorolac Clearance n = 8	R+ Ketorolac Clearance n = 8	Placebo n = 0
Value	30.7 (22.8)	6.5 (2.2)	–

Population analysed: of 25 infants aged 2-6 months enrolled, 11 were excluded. 8 received drug, 6 received placebo; this is a subset of the 77 enrolled infants (aged 2-18 months) of whom 51 completed the study. Infants receiving drug at 0.5 or 1 mg/kg were reported together, since no difference in drug handling was seen.

Primary outcome: Central Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Time frame: 24 hours after surgery. Mean (Standard Error). Unit: ml

Measure	S- Ketorolac Volume Distribution, Central n = 8	R+ Ketorolac Volume Distribution, Central n = 8	Placebo n = 0
Value	1480 (920)	992 (440)	–

Population analysed: infants enrolled but did not complete protocol if abnormal laboratory studies or intravenous catheters were not functioning prior to study drug infusion. Of 77 enrolled, 51 completed study; of the 33 given ketorolac,8 were aged 2-6 months. Doses of 0.5 or 1 mg/kg were handled similarly so reported together.

Primary outcome: Peripheral Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Time frame: 24 hours post surgery. Mean (Standard Deviation). Unit: ml

Measure	S- Ketorolac Volume Distribution, Peripheral n = 8	R+ Ketorolac Volume Distribution, Peripheral n = 8	Placebo n = 0
Value	341 (342)	658 (207)	–

Population analysed: 25 infants aged 2-6 months enrolled; 11 excluded for no sampling intravenous access. 8 infants received drug, 6 received placebo. No difference in analysis of doses of 0.5 or 1 mg/kg so reported together.

Primary outcome: Half-life of S- and R+ Ketorolac in 2-6 Month Old Infants

Time frame: 24 hours after surgery. Mean (Standard Error). Unit: min

Measure	S- Ketorolac Half-life n = 8	R+ Ketorolac Half-life n = 8	Placebo n = 0
Value	67 (33)	197 (82)	–

Population analysed: total infants enrolled was 77; 26 were excluded before study procedures began. Of 51 infants completing the study, 8 infants aged 2-6 months received drug.No difference in analysis at doses of 0.5 or 1 mg/kg so reported together.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 hours following surgery, monitoring for oximetry, blood loss, renal and liver function tests were done after drug infusion (active drug or placebo). Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketorolac 1 mg/kg Intravenous	0 of 22 (0%)	0 of 22 (0%)	Not reported
Ketorolac 0.5 mg/kg Intravenous	0 of 11 (0%)	0 of 11 (0%)	Not reported
Dextrose 5% in Water (D5W)	0 of 18 (0%)	0 of 18 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 17456651Lynn 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.
Results publication: PubMed 21199130Lynn 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Anne M. Lynn, MD principal investigator

Seattle Children's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery (time frame: 24 hours following surgery). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01260883, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2013.

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (1 listed)

Key exclusion criteria (5 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery

Primary outcome: Central Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Primary outcome: Peripheral Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Primary outcome: Half-life of S- and R+ Ketorolac in 2-6 Month Old Infants

Adverse events

Research links

Related trials for Postoperative Pain in Infants

Postoperative Pain in Infants

Clonidine in Ultrasound-guided Rectus Sheath Block for Outpatient Umbilical Hernioplasty

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Clearance of S-ketorolac and R+ Ketorolac in 2-6 Month Old Infants Following Surgery

Primary outcome: Central Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Primary outcome: Peripheral Volume of Distribution for S- and R+ Ketorolac in 2-6 Month Old Infants

Primary outcome: Half-life of S- and R+ Ketorolac in 2-6 Month Old Infants

Adverse events