Intranasal Ketorolac Trial

NCT06083571 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 202307050
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Headache, Migraine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Response Rate- 2/10 score difference of pain on the Faces Pain Scale- Revised

  10 minutes after medication given

Study Arms (2)

Intranasal Patients

EXPERIMENTAL

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; Drug: Prochlorperazine; Drug: Diphenhydramine

Intravenous Patients

ACTIVE COMPARATOR

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; Drug: Prochlorperazine; Drug: Diphenhydramine

Interventions

Ketorolac DRUG

Non-inferiority

Also known as: Sprix

Intranasal Patients; Intravenous Patients

Prochlorperazine DRUG

Adjunct

Also known as: Compazine

Intranasal Patients; Intravenous Patients

Diphenhydramine DRUG

Adjunct

Also known as: Benadryl

Intranasal Patients; Intravenous Patients

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Assertio Holdings, Inc: collaborator

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Kuensting LL, DeBoer S, Holleran R, Shultz BL, Steinmann RA, Venella J. Difficult venous access in children: taking control. J Emerg Nurs. 2009 Sep;35(5):419-24. doi: 10.1016/j.jen.2009.01.014. Epub 2009 Mar 21. No abstract available.

  PMID: 19748021 BACKGROUND

• Tsze DS, Lubell TR, Carter RC, Chernick LS, DePeter KC, McLaren SH, Kwok MY, Roskind CG, Gonzalez AE, Fan W, Babineau SE, Friedman BW, Dayan PS. Intranasal ketorolac versus intravenous ketorolac for treatment of migraine headaches in children: A randomized clinical trial. Acad Emerg Med. 2022 Apr;29(4):465-475. doi: 10.1111/acem.14422. Epub 2021 Dec 13.

  PMID: 34822214 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders

Interventions

Ketorolac; Prochlorperazine; Diphenhydramine

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Sophia Rifkin, MD

  Washington University in St. Louis: st. louis childrens hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: October 16, 2023
• Study Start: January 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)