Oral Medications for the Management of Acute Migraine Headache in the Emergency Department

Acute Migraine Headache Clinical Trial

Official title:

Oral v. Parenteral Medications for the Emergency Management of Acute Migraine: a Pilot Randomized Control Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05983354
• Other study ID #: 23-016
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: June 30, 2024

Study information

• Verified date: July 2023
• Source: Health Sciences North Research Institute
• Contact: Robert Ohle, MBBCh
• Phone: (705) 523-7100
• Email: robert.ohle[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this pilot randomized control trial is to assess the feasibility of our patient recruitment and data collection strategy ahead of a full scale RCT investigating the efficacy of oral v. parenteral medications in the management of acute migraine headaches in the emergency department. Patients will be randomly assigned to receive either (A) standard medical therapy for the treatment of acute migraine headache (metoclopramide and ketorolac IV) and oral placebo or (B) oral metoclopramide and ibuprofen with normal saline IV. Primary outcome measures are recruitment rate and improvement in pain score at 60 minutes from medication administration.

Description:

Objectives

The planned study is a pilot study designed to assess the feasibility of our recruitment and data collection strategy. The primary feasibility outcome will be recruitment rate, which is defined as the proportion of eligible patients approached who are successfully recruited over the proposed 6-month pilot study period. Our secondary feasibility outcomes are (a) proportion of eligible patients approached and (b) rate of attrition during the study period.

Our preliminary primary outcome will be improvement in pain from baseline to 60 minutes after medication administration using the visual analogue scale (Bijur et al. 2008). Preliminary secondary outcomes will include headache relief and freedom from headache at 2 h, the need for rescue medication, ED length of stay and return to ED within 24h of discharge. The frequency of adverse effects, including gastrointestinal upset, patient-reported restlessness or dystonic reaction and fatigue, will be assessed.

Design

In this parallel, noninferiority, double-blind randomised control pilot study, eligible patients presenting to the emergency department with a chief complaint of headache will be randomly assigned with an allocation ratio of 1:1 to receive one of 2 treatments: intravenous ketorolac (10 mg) and metoclopramide (10 mg) v. oral ibuprofen (400 mg) and metoclopramide (10 mg). Dosing was selected to reflect the lowest effective doses recommended for emergency department management of migraine headaches (Friedman et al. 2011, Motov et al. 2017). The study will last 6 months at which time it will stop.

Study population

Patients between the ages of 18 and 64 presenting to the ED with a chief complaint of headache will be eligible to participate in the study. Exclusion criteria include vomiting or inability to tolerate oral medications at the time of medication administration, focal neurologic symptoms, head trauma within 14 days, history of renal disease, contraindication to NSAIDs including pregnancy or concurrent use of blood thinners, hypersensitivity reaction to any of the study medications, or >15 headache days per month.

Study procedures

Treatment will be assigned using a random number generator. Contents of treatment, which will be identical in appearance, will be known only to the research pharmacist and this information will be stored remotely from the ED. Administering nurses and treating physicians will be blind to the treatment group, as will patients and research assistants collecting outcome data.

Data collection

Data will be collected using patient interviews immediately prior to medication administration and repeated at 1 and 2 hours after medication administration. A chart review will then be conducted to check for return visits within 24 h of ED discharge.

Enrolment:

Based on sample size calculations, 55 patients will be enrolled.

Statistical procedures:

Primary and secondary feasibility outcomes will be reported as the proportion of patients approached who were recruited, proportion of eligible patients approached and the proportion who withdrew consent during the study period +/- 95% CI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Presentation to emergency department with headache

Exclusion Criteria:

• Vomiting or unable to tolerate PO at tie of med admin

• Focal neurologic symptoms

• Head trauma within 14d

• Pregnancy

• Concurrent use of blood thinners

• Hypersensitivity reaction to any of the study medications

• >14 HA days per month

Related Conditions & MeSH terms

• Acute Migraine Headache
• Emergencies
• Headache
• Migraine Disorders

Intervention

Drug:
• Oral metoclopramide and ibuprofen
10 mg oral metoclopramide, 400 mg oral ibuprofen with 2 x 50 ml normal saline IV administered over 15 minutes.
• Intravenous metoclopramide and ketorolac
10 mg of metoclopramide IV in 50 ml normal saline, 10 mg ketorolac IV in 50 ml normal saline administered over 15 minutes, with 2 placebo tablets.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Health Sciences North Research Institute

References & Publications (7)

Azzopardi TD, Brooks NA. Oral metoclopramide as an adjunct to analgesics for the outpatient treatment of acute migraine. Ann Pharmacother. 2008 Mar;42(3):397-402. doi: 10.1345/aph.1K481. Epub 2008 Feb 19. — View Citation

Bijur PE, Silver W, Gallagher EJ. Reliability of the visual analog scale for measurement of acute pain. Acad Emerg Med. 2001 Dec;8(12):1153-7. doi: 10.1111/j.1553-2712.2001.tb01132.x. — View Citation

Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys. Headache. 2021 Jan;61(1):60-68. doi: 10.1111/head.14024. Epub 2020 Dec 21. — View Citation

Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache. 2015 Jan;55(1):21-34. doi: 10.1111/head.12482. Erratum In: Headache. 2015 Feb;55(2):356. — View Citation

Friedman BW, Mulvey L, Esses D, Solorzano C, Paternoster J, Lipton RB, Gallagher EJ. Metoclopramide for acute migraine: a dose-finding randomized clinical trial. Ann Emerg Med. 2011 May;57(5):475-82.e1. doi: 10.1016/j.annemergmed.2010.11.023. Epub 2011 Jan 12. — View Citation

Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16. — View Citation

Yeh WZ, Blizzard L, Taylor BV. What is the actual prevalence of migraine? Brain Behav. 2018 Jun;8(6):e00950. doi: 10.1002/brb3.950. Epub 2018 May 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Proportion of eligible patients presenting to ED who are successfully recruited	6 months
Primary	Pain relief	Change in visual analogue scale (0-10 where 0 is no pain and 10 is maximal pain) from baseline to 60 minutes after medication administration	60 minutes
Secondary	Proportion of eligible patients approached	Proportion of all eligible patients who were approached by research assistants	6 months
Secondary	Rate of attrition during the study period	Number of patients recruited to study who ended participation during study period	24 hours
Secondary	Pain relief at 2 hours	Change in visual analogue scale from baseline to 120 minutes after medication administration	120 minutes
Secondary	Freedom from headache	Patients who report complete resolution of headache at 60 minutes from medication administration	60 minutes
Secondary	Need for rescue medication	Additional medications administered by treating physician after 60 minutes	24 h
Secondary	Emergency department length of stay	Time from initial physician assessment to discharge	24 hours
Secondary	Return to emergency department	Patients who were registered again to the ED within 24 hours of discharge	24 hours
Secondary	Adverse reactions	Any adverse reaction reported during the study period	24 hours