Trial Outcomes & Findings for Intranasal Ketorolac Versus Intravenous Ketorolac for Treatment of Migraine Headaches in Children (NCT NCT02358681)

NCT ID: NCT02358681

Last Updated: 2022-01-12

Results Overview

Measure the change in pain score after administration of analgesic using the Faces Pain Scale - Revised (FPS-R) at 60 minutes after analgesic administration. The FPS-R is scored from 0 (no pain) to 10 (maximum pain intensity, i.e. worst outcome).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 59 participants
• Primary outcome timeframe: 60 minutes
• Results posted on: 2022-01-12

Participant Flow

Participant milestones

Measure	Ketorolac, Intranasal 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Overall Study STARTED	29	30
Overall Study COMPLETED	27	29
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intranasal Ketorolac Versus Intravenous Ketorolac for Treatment of Migraine Headaches in Children

Baseline characteristics by cohort

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.	Total n=56 Participants Total of all reporting groups
Age, Continuous	14 years n=5 Participants	15 years n=7 Participants	14.5 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Don't know	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 60 minutes

Measure the change in pain score after administration of analgesic using the Faces Pain Scale - Revised (FPS-R) at 60 minutes after analgesic administration. The FPS-R is scored from 0 (no pain) to 10 (maximum pain intensity, i.e. worst outcome).

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Change in Pain Score After Analgesic Administration (Faces Pain Scale - Revised (FPS-R)	4.2 units on a scale Interval 3.6 to 4.8	4.4 units on a scale Interval 3.5 to 5.3

SECONDARY outcome

Timeframe: 10, 30, 60 and 120 minutes

Pain score will be assessed at 10, 30, 60 and 120 minutes after analgesic administration, until pain score decreases by 2/10 on the Faces Pain Scale - Revised (FPS-R). The FPS-R is scored from 0 (no pain) to 10 (maximal pain, i.e. worst outcome)

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Time to Achieve Clinically Significant Reduction in Pain After Analgesic Administration (Pain Score)	21.9 Minutes Interval 15.0 to 28.8	18.6 Minutes Interval 12.7 to 25.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Adverse events will be assessed at the 1- and 2-hour assessments and the 24-hour follow up.

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Adverse Events	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 hours

Rescue medication defined as an additional parenteral analgesic administered in response to inadequate improvement in pain. Rescue medication was administered when deemed clinically indicated by the treating clinician.

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Received Rescue Medications During Emergency Department Visit	6 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 hours

Headache relief defined as change of the patient's headache pain intensity from severe to moderate to either mild or none, without receipt of rescue medications.

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Experienced Headache Relief During Emergency Department Visit	25 Participants	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 hours

Headache freedom defined as achieving a headache pain intensity of "none", without receipt of rescue medications.

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Experienced Headache Freedom During Emergency Department Visit	11 Participants	17 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 hour

Percentage change in pain score between baseline and one hour after study medication administration. Pain measured using the Faces Pain Scale - Revised (FPS-R), which is scored from 0 (no pain) to 10 (maximum pain intensity, i.e. worst outcome). Positive values (i.e. percentage change) indicate a DECREASE (i.e. improvement) in pain intensity.

Outcome measures

Measure	Ketorolac, Intranasal n=27 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Percentage Change in Pain Score Between Baseline and One Hour	69.8 percentage of initial pain intensity Interval 60.6 to 78.9	71.8 percentage of initial pain intensity Interval 60.7 to 82.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Patient's assessment of overall efficacy and tolerability was assessed by asking the question, "The next time you come to the emergency department with a headache or migraine, do you want to be given the same medication?". A "yes" response was considered positive assessment of overall efficacy and tolerability.

Outcome measures

Measure	Ketorolac, Intranasal n=24 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=22 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Reported Positive Overall Efficacy and Tolerability at 24-hour Follow-up	19 Participants	21 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Sustained headache freedom defined as achieving headache freedom (i.e. headache pain intensity of "none"), and maintaining this level for 24 hours without the use of rescue medications after emergency department discharge.

Outcome measures

Measure	Ketorolac, Intranasal n=24 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=23 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Reported Sustained Headache Freedom at 24-hour Follow-up	7 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Sustained headache relief defined as achieving headache relief (i.e. headache pain intensity of "mild" or "none") and maintaining this level for 24 hours without the use of rescue medications after emergency department discharge.

Outcome measures

Measure	Ketorolac, Intranasal n=24 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=23 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Reported Sustained Headache Relief at 24-hour Follow-up	7 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Rescue medications used after emergency department discharged defined as an analgesic taken by the participant at home to reduce pain associated with their headache.

Outcome measures

Measure	Ketorolac, Intranasal n=18 Participants 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=19 Participants 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Number of Participants Who Used Rescue Medication(s) Within 24 Hours After Emergency Department Discharge	12 Participants	8 Participants

Adverse Events

Ketorolac, Intranasal

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Ketorolac, Intravenous

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ketorolac, Intranasal n=27 participants at risk 1. Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose. 2. Placebo, intravenous. Ketorolac, intranasal: Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route. Placebo, intravenous: Placebo of equal volume to IV ketorolac, to be administered by intravenous route.	Ketorolac, Intravenous n=29 participants at risk 1. Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose. 2. Placebo, intranasal. Ketorolac, intravenous: Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route. Placebo, intranasal: Placebo of equal volume to IN ketorolac, to be administered by intranasal route.
Gastrointestinal disorders Nausea	7.4% 2/27 • 24 hours after discharge from emergency department.	3.4% 1/29 • 24 hours after discharge from emergency department.
Nervous system disorders Dizziness	3.7% 1/27 • 24 hours after discharge from emergency department.	3.4% 1/29 • 24 hours after discharge from emergency department.
Nervous system disorders Sleepiness	0.00% 0/27 • 24 hours after discharge from emergency department.	3.4% 1/29 • 24 hours after discharge from emergency department.
Nervous system disorders Other	7.4% 2/27 • 24 hours after discharge from emergency department.	10.3% 3/29 • 24 hours after discharge from emergency department.

Additional Information

Daniel Tsze MD MPH

Columbia University

Phone: 212-317-0997

Email: dst2141@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place