Intranasal Ketorolac Trial

The Washington University

Status and phase: Terminated; Phase 2

Conditions: Headache, Migraine

Treatments: Drug: Diphenhydramine; Drug: Ketorolac; Drug: Prochlorperazine

Study type: Interventional

Funder types: Other

Identifiers

NCT06083571

202307050

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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41 participants in 2 patient groups

Intranasal Patients

Experimental group

Description:

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)

Treatment:

Drug: Prochlorperazine

Drug: Ketorolac

Drug: Diphenhydramine

Intravenous Patients

Active Comparator group

Description:

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)

Treatment:

Drug: Prochlorperazine

Drug: Ketorolac

Drug: Diphenhydramine