Intranasal Ketorolac Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine if intranasal (IN) Ketorolac in combination with oral Prochlorperazine and Diphenhydramine is non-inferior to current migraine management which involves use of intravenous (IV) Ketorolac and oral adjuncts Prochlorperazine and diphenhydramine for reducing pain intensity in children with migraine headaches. The investigators hypothesize that IN ketorolac combined with these oral adjuncts is non-inferior to IV ketorolac and oral adjuncts in reducing acute migraine headache pain by a minimum clinically significant difference within 60 minutes of administration.

Official Title
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Efficacy of Nasal Migraine Cocktail Used In Pediatric Emergency Department: A Clinical Trial

Conditions
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Headache, Migraine

Intervention / Treatment
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* Drug: Ketorolac
* Drug: Prochlorperazine
* Drug: Diphenhydramine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A headache that fulfills at least three of the six following criteria: i) moderate to severe episode of impaired daily activities; ii) focal localization of headache (focal meaning unilateral, bifrontal, bitemporal, or biparietal); iii) pulsatile description; iv) nausea or vomiting or abdominal pain; v) photophobia or phonophobia or avoidance of light and noise; and vi) symptoms increasing with activity or resolving by rest Pain 4/10 on the validated Faces Pain Scale Headache duration between 1 and 72 hours Exclusion Criteria: Any contraindication to receiving ketorolac (e.g. known allergy, known peptic ulcer disease, gastrointestinal bleeding, hepatic impairment (patients with known aspartate aminotransferase (AST) > 60 units/L OR alanine aminotransferase (ALT) > 40 units/L OR total bilirubin > 1.2 mg/dl) Renal impairment (patients with known estimated glomerular filtration rate of < 90 mL/min/1.73m2) Known bleeding disorders Receipt of an NSAID (e.g. ibuprofen, naproxen, naproxen/sumatriptan) within previous six hours Receipt of oral prochlorperazine or metoclopramide or diphenhydramine within 12 hours prior to presentation Presence of intranasal obstruction (e.g. mucous or blood) that cannot be readily cleared using suction or nose blowing Inability to speak English Patients with a concurrent diagnosis of traumatic brain injury Unable to complete self-report measures of pain or questionnaires (e.g. developmental delay, neurologic impairment) Critical illness Frequent use of drugs for headache (defined as regular intake of analgesics for acute headaches on more than 10 days per month) Patients refusing to take oral adjuncts or unable to tolerate oral medications will be excluded from the trial. Patients currently on the following medications will also be excluded from the study as there are contraindications for use of Ketorolac with use of these medications: antiplatelets (i.e. salicylates, aspirin, clopidogrel, ticagrelor), Anticoagulants (i.e. warfarin, rivaroxaban, apixaban, dabigatran, enoxaparin, and heparin), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (losartan, Lisinopril), cyclosporine or tacrolimus, furosemide, bumetanide, spironolactone, hydrochlorothiazide, digoxin, lithium, methotrexate, probenecid, some selective serotonin reuptake inhibitors (including i.e. citalopram, escitalopram, sertraline), antipsychotics (i.e. Quetiapine, risperidone, aripiprazole, haloperidol), tranylcypromine, oxybates, oral potassium citrate, and Anticholinergics (i.e. amantadine).

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal Patients<br>Intranasal ketorolac (1 spray (15.75mg) if 15kg-29.9kg and 2 sprays (31.5mg) if 30kg or heavier and oral adjuncts oral Prochlorperazine (Between 15-25 kg: dose of 2.5 mg; 26-50 kg: dose of 5 mg; > 50 kg: dose of 10 mg, single maximum dose 10 mg) and oral Diphenhydramine (Between 15-25 kg: dose of 12.5 mg; 26-50 kg: dose of 25 mg; > 50 kg: dose of 50 mg, single maximum dose 50mg) | Drug: Ketorolac<br>* Non-inferiority<br>* Other names: Sprix;Drug: Prochlorperazine<br>* Adjunct<br>* Other names: Compazine;Drug: Diphenhydramine<br>* Adjunct<br>* Other names: Benadryl;|
| Active Comparator: Intravenous Patients<br>IV ketorolac (0.5 mg/kg, maximum single dose of 30 mg) with oral adjuncts oral Prochlorperazine (Between 15-25 kg: dose of 2.5 mg; 26-50 kg: dose of 5 mg; > 50 kg: dose of 10 mg, single maximum dose 10 mg) and oral Diphenhydramine (Between 15-25 kg: dose of 12.5 mg; 26-50 kg: dose of 25 mg; > 50 kg: dose of 50 mg, single maximum dose 50mg) | Drug: Ketorolac<br>* Non-inferiority<br>* Other names: Sprix;Drug: Prochlorperazine<br>* Adjunct<br>* Other names: Compazine;Drug: Diphenhydramine<br>* Adjunct<br>* Other names: Benadryl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pain on the 10 point Faces Pain Scale-Revised in 2 hours | The Faces Pain Scale - Revised. This is a 10-point pain scale (0-10) that has been validated for the use in children greater than 4 years of age in the ED; is one of the self-report measures of pain recommended for research in children; and is commonly used as the primary outcome in Emergency Department research. Lower numbers are better outcomes. | Baseline (within 15 minutes prior to receiving the study drug or as close to this time frame as possible) and then at 10 minutes, 30 minutes, 60 minutes, and 120 minutes (or as close to this time frame as possible) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate- 2/10 score difference of pain on the Faces Pain Scale- Revised | Response rate is defined as the number of participants with a pain scale change of at least 2/10 on The Faces Pain Scale - Revised from baseline to 10 minutes after medication given. The Faces Pain Scale - Revised. The Faces Pain Scale - Revised is a 10-point pain scale that has been validated for the use in children greater than 4 years of age in the Emergency Department; is one of the self-report measures of pain recommended for research in children; and is commonly used as the primary outcome in Emergency Department research. The lower numbers on this scale report better outcomes. | 10 minutes after medication given |