Intranasal Ketorolac Trial

Sponsor

Washington University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06083571

Collaborator

Assertio Holdings, Inc (Other)

120

Enrollment

Arms

26.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Headache, Migraine	Drug: Ketorolac Drug: Prochlorperazine Drug: Diphenhydramine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 15, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal Patients 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 Non-inferiority Other Names: Sprix Drug: Prochlorperazine Adjunct Other Names: Compazine Drug: Diphenhydramine Adjunct Other Names: Benadryl
Active Comparator: Intravenous Patients 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 Non-inferiority Other Names: Sprix Drug: Prochlorperazine Adjunct Other Names: Compazine Drug: Diphenhydramine Adjunct Other Names: Benadryl

Arm

Intervention/Treatment

Experimental: Intranasal Patients

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

Non-inferiority

Other Names:

Sprix

Drug: Prochlorperazine

Adjunct

Other Names:

Compazine

Drug: Diphenhydramine

Adjunct

Other Names:

Benadryl

Active Comparator: Intravenous Patients

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

Non-inferiority

Other Names:

Sprix

Drug: Prochlorperazine

Adjunct

Other Names:

Compazine

Drug: Diphenhydramine

Adjunct

Other Names:

Benadryl

Outcome Measures

Primary Outcome Measures

Change from baseline in pain on the 10 point Faces Pain Scale-Revised in 2 hours [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)]
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.

Secondary Outcome Measures

Response Rate- 2/10 score difference of pain on the Faces Pain Scale- Revised [10 minutes after medication given]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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;

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).