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.

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.

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

Treatment will be randomly assigned using a random number generator by an independent research assistant who is not involved in data collection. Contents of treatment will be known only to the research pharmacist and this information will be stored remotely from the ED; patients, administering nurses and treating physicians will be blind to the treatment group, as well the research assistants collecting outcome data.