Clinical trial NCT02358681: Intranasal Ketorolac Versus Intravenous Ketorolac for Treatment of Migraine Headaches in Children
Official title: Intranasal Ketorolac Versus Intravenous Ketorolac for Treatment of Migraine Headaches in Children: A Randomized Non-inferiority Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Keywords: Intranasal
Ketorolac
Pediatric
Migraine
Headache
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Migraine Research Foundation
First posted: 2015-02-09
Enrollment: 59
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Pain Score After Analgesic Administration (Faces Pain Scale - Revised (FPS-R)
timeFrame: 60 minutes
Secondary outcomes:
measure: Time to Achieve Clinically Significant Reduction in Pain After Analgesic Administration (Pain Score)
timeFrame: 10, 30, 60 and 120 minutes
Other outcomes:
measure: Adverse Events
timeFrame: 24 hours
measure: Number of Participants Who Received Rescue Medications During Emergency Department Visit
timeFrame: 12 hours
measure: Number of Participants Who Experienced Headache Relief During Emergency Department Visit
timeFrame: 2 hours
measure: Number of Participants Who Experienced Headache Freedom During Emergency Department Visit
timeFrame: 2 hours
measure: Percentage Change in Pain Score Between Baseline and One Hour
timeFrame: 1 hour
measure: Number of Participants Who Reported Positive Overall Efficacy and Tolerability at 24-hour Follow-up
timeFrame: 24 hours
measure: Number of Participants Who Reported Sustained Headache Freedom at 24-hour Follow-up
timeFrame: 24 hours
measure: Number of Participants Who Reported Sustained Headache Relief at 24-hour Follow-up
timeFrame: 24 hours
measure: Number of Participants Who Used Rescue Medication(s) Within 24 Hours After Emergency Department Discharge
timeFrame: 24 hours
Locations:
city: New York
country: United States
facility: NewYork Presbyterian Morgan Stanley Children's Hospital
state: New York
Study officials:
affiliation: Columbia University
name: Daniel S Tsze, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: