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Intranasal Ketorolac Trial

Primary Purpose

Headache, Migraine

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ketorolac
Prochlorperazine
Diphenhydramine
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Headache, Migraine

Eligibility Criteria

6 Years - 17 Years (Child)All SexesAccepts 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).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Intranasal Patients

    Intravenous Patients

    Arm 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)

    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)

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.

    Full Information

    First Posted
    September 18, 2023
    Last Updated
    October 11, 2023
    Sponsor
    Washington University School of Medicine
    Collaborators
    Assertio Holdings, Inc
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06083571
    Brief Title
    Intranasal Ketorolac Trial
    Official Title
    Efficacy of Nasal Migraine Cocktail Used In Pediatric Emergency Department: A Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 15, 2023 (Anticipated)
    Primary Completion Date
    July 1, 2025 (Anticipated)
    Study Completion Date
    January 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Washington University School of Medicine
    Collaborators
    Assertio Holdings, Inc

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Headache, Migraine

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    120 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intranasal Patients
    Arm Type
    Experimental
    Arm 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)
    Arm Title
    Intravenous Patients
    Arm Type
    Active Comparator
    Arm 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)
    Intervention Type
    Drug
    Intervention Name(s)
    Ketorolac
    Other Intervention Name(s)
    Sprix
    Intervention Description
    Non-inferiority
    Intervention Type
    Drug
    Intervention Name(s)
    Prochlorperazine
    Other Intervention Name(s)
    Compazine
    Intervention Description
    Adjunct
    Intervention Type
    Drug
    Intervention Name(s)
    Diphenhydramine
    Other Intervention Name(s)
    Benadryl
    Intervention Description
    Adjunct
    Primary Outcome Measure Information:
    Title
    Change from baseline in pain on the 10 point Faces Pain Scale-Revised in 2 hours
    Description
    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.
    Time Frame
    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 Measure Information:
    Title
    Response Rate- 2/10 score difference of pain on the Faces Pain Scale- Revised
    Description
    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.
    Time Frame
    10 minutes after medication given

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    6 Years
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Carlee Lenehan, MD
    Phone
    3529018388
    Email
    carleel@wustl.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Carlee Lenehan, MD
    Organizational Affiliation
    Washington University in St. Louis: st. louis childrens hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    19748021
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    34822214
    Citation
    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.
    Results Reference
    background

    Learn more about this trial

    Intranasal Ketorolac Trial

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