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

Intranasal Ketorolac Versus Intravenous Ketorolac for Treatment of Migraine Headaches in Children: A Randomized Non-inferiority Clinical Trial

Ketorolac is an evidence-based, first-line acute migraine therapy that is commonly used in the pediatric population; however, it is typically administered by the intravenous (IV) or intramuscular (IM) routes, both of which require a painful and distressing needle stick to administer.

The intranasal (IN) route is a painless and effective way of administering analgesics, including ketorolac: IN ketorolac has been shown to be an effective analgesic in adults for painful conditions, including acute migraine headaches. However, IN ketorolac has been understudied in children, and it is not known how effective it is compared to IV ketorolac, which is currently the most common way of administering ketorolac to children. If IN ketorolac is shown to be no less effective than IV ketorolac, IN ketorolac may be a viable and painless alternative to effectively treat acute migraine headaches in children.

Therefore, our primary aim is to demonstrate that IN ketorolac is non-inferior to IV ketorolac for reducing pain in children with acute migraine headaches.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Ketorolac, intranasal; Drug: Placebo, intravenous; Drug: Ketorolac, intravenous; Drug: Placebo, intranasal

Detailed Description

Primary Aim: Determine whether intranasal (IN) ketorolac is non-inferior to intravenous (IV) ketorolac for reducing pain in children with acute migraine headaches. We hypothesize that IN ketorolac is non-inferior to IV ketorolac in reducing acute migraine headache pain by a minimum clinically significant difference within 60 minutes of administration.

Secondary Aim: Determine whether there is a difference in time to achieve a clinically significant reduction in pain after receiving IN ketorolac compared to IV ketorolac. We hypothesize that there is no difference between IN ketorolac and IV ketorolac in the time it takes to achieve a clinically significant reduction in pain.

We will conduct a prospective, double-blinded, randomized, non-inferiority, parallel 1:1 clinical trial of eligible children in a single urban pediatric ED. We will block randomize patients to receive either 1 mg/kg IN ketorolac and an IV placebo (study group A), or 0.5 mg/kg IV ketorolac and an IN placebo (study group B).

We will assess the patient's pain at baseline, and then at 10 minutes, 30 minutes and 60 minutes after administration of the study drug. The patient will then be assessed at 2 hours and 24 hours after study drug administration for outcomes related to efficacy, function, and safety.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • NewYork Presbyterian Morgan Stanley Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Present to the emergency department with a migraine headache as defined by the modified Irma criteria. The modified Irma criteria are as follows: Headache episodes of 1-168 hours (7 days) presenting with at least 3 of the following 6 criteria: moderate to severe episode of impaired daily activities; focal localization of headache; pulsatile description; nausea or vomiting or abdominal pain; photophobia or phonophobia or avoidance of light and noise; symptoms increasing with activity or resolving by rest.
• Headache severity of moderate to severe pain (i.e. at least 4/10 on the Faces Pain Scale - Revised)
• Requiring IV fluids and any IV medication (for example: ketorolac, metoclopramide, prochlorperazine, ondansetron) as part of their headache treatment, as per their treating attending physician

Exclusion Criteria:

• Contraindication to receiving ketorolac
• Receipt of an NSAID within six hours of study drug administration
• Presence of an intranasal obstruction that cannot be readily cleared
• Inability to speak English or Spanish
• Unable to complete self-report measures of pain or questionnaires
• Critical illness
• Frequent use of drugs for headache (i.e. regular intake of analgesics for acute headaches on more than 10 days per month).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketorolac, intranasal; Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route, single dose.; Placebo, intravenous.	Drug: Ketorolac, intranasal; Ketorolac 1 mg/kg, maximum dose 30 mg. To be administered by intranasal route.; Other Names: Toradol; Drug: Placebo, intravenous; Placebo of equal volume to IV ketorolac, to be administered by intravenous route.
Active Comparator: Ketorolac, intravenous; Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route, single dose.; Placebo, intranasal.	Drug: Ketorolac, intravenous; Ketorolac 0.5 mg/kg, maximum dose 30 mg. To be administered by intravenous route.; Other Names: Toradol; Drug: Placebo, intranasal; Placebo of equal volume to IN ketorolac, to be administered by intranasal route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Score After Analgesic Administration (Faces Pain Scale - Revised (FPS-R)	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).	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Achieve Clinically Significant Reduction in Pain After Analgesic Administration (Pain Score)	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)	10, 30, 60 and 120 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse events will be assessed at the 1- and 2-hour assessments and the 24-hour follow up.	24 hours
Number of Participants Who Received Rescue Medications During Emergency Department Visit	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.	12 hours
Number of Participants Who Experienced Headache Relief During Emergency Department Visit	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.	2 hours
Number of Participants Who Experienced Headache Freedom During Emergency Department Visit	Headache freedom defined as achieving a headache pain intensity of "none", without receipt of rescue medications.	2 hours
Percentage Change in Pain Score Between Baseline and One 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.	1 hour
Number of Participants Who Reported Positive Overall Efficacy and Tolerability at 24-hour Follow-up	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.	24 hours
Number of Participants Who Reported Sustained Headache Freedom at 24-hour Follow-up	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.	24 hours
Number of Participants Who Reported Sustained Headache Relief at 24-hour Follow-up	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.	24 hours
Number of Participants Who Used Rescue Medication(s) Within 24 Hours After Emergency Department Discharge	Rescue medications used after emergency department discharged defined as an analgesic taken by the participant at home to reduce pain associated with their headache.	24 hours

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Migraine Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2015
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 9, 2015

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 3, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Pediatric; Migraine; Headache; Intranasal; Ketorolac
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: AAAO1302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No