Migraine
Conditions
Brief summary
Migraine recurrence is common amongst pediatric patients being discharged from the emergency department after treatment for migraine. Despite the commonality of migraine recurrence within the week following discharge, no known effective therapies are available in the pediatric population, though dexamethasone has been established as efficacious in the adult migraine population. The proposed study will randomly assign children and adolescents visiting the emergency department (ED) for migraine to receive either one dose of oral dexamethasone or oral placebo. Twenty patients will be recruited to this randomized, double-blind, pilot trial over a 6 month period, and the aim of the study will be to determine the feasibility and acceptability of the protocol.
Detailed description
Migraine is common in the pediatric emergency department. Unfortunately, somewhere between one third and two thirds of children and adolescents will have recurrence of their migraine within a week of discharge from the emergency department. Although there is strong evidence from adult studies that dexamethasone can prevent migraine recurrence, there is no evidence on how to prevent recurrence in children and adolescents. The proposed study will randomly assign children and adolescents visiting the Children's Hospital of Eastern Ontario (CHEO) emergency department (ED) for migraine to receive either one dose of oral dexamethasone or oral placebo. Twenty patients will be recruited to this randomized, double-blind, pilot trial over a 6 month period, and the aim of the study will be to determine the feasibility and acceptability of the protocol. Patients will be recruited from the CHEO ED. Research volunteers will screen patients with a triage diagnosis of 'headache', 'migraine' or a related triage diagnosis for eligibility. Patients who meet eligibility criteria will be approached by a research assistant who will initiate the consent process. Informed consent will be sought through both verbal explanation and in written form, from participants 14 years and over and from the parent(s) or guardian(s). For participants under the age of 14 years, verbal and written assent will be sought. Consenting participants will be randomized to receive one dose of oral dexamethasone 0.6mg/kg to a maximum of 15mg or one dose of oral matched placebo. Randomization will be stratified by baseline migraine duration: 1) less than 2 hours, 2) 2 hours to less than 24 hours and 3) 24 hours and greater. A list of randomization codes will be generated over the computer by a biostatistician and randomization will occur in blocks of four. Research personnel will not have access to the randomization code list with group assignments. Only the research pharmacists will have access to the list. The research assistants will collect outcome data from the participants and store it into Research Electronic Data Capture (REDCaP), a secure, encrypted web-based platform. Participants will have the option of completing follow-up via email questionnaires or over the telephone. Follow-up will take place 48 hours and 7 days after discharge. The purpose of follow-up will be to assess whether or not participants had recurrence of their migraine, and to collect other follow-up outcome data and safety data. The research assistants, participants, research personnel and clinical personnel will all be blinded to group assignment. Only the research pharmacists, who will not interact with anyone in the study directly, will have access to group assignment information. Data analyses will be carried out for exploratory purposes, and the groups (dexamethasone vs. placebo) will be compared with regards to: baseline data, 48 hour migraine recurrence rates, 7 day migraine recurrence rates, the proportion of participants achieving pain freedom at 2 hours and maintaining it at 48 hours, patient satisfaction data and adverse events.
Interventions
DRUGDexamethasone
Dexamethasone 0.6mg/kg (maximum 15mg) PO x 1 dose
OTHERPlacebo
Matched oral solution
Sponsors
The Physicians' Services Incorporated Foundation
Children's Hospital of Eastern Ontario
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Between the ages of 8 and 18 years (ie. \> 8.0 years and \< 18.0 years) 2. Diagnosed with migraine according to a modified version of International Classification of Headache Disorders 3rd edition (ICHD-3, beta version) where criterion A (ie. minimum of 5 prior episodes meeting criteria B-D) has been removed to increase sensitivity of diagnosis in the emergency department setting
Exclusion criteria
1. Received a dose of a steroid medication in the past 7 days 2. Known allergy to dexamethasone 3. Immunosuppressed 4. Cushing's syndrome 5. Known diabetes mellitus 6. Known peptic or duodenal ulcer or other major gastrointestinal illness (ex. ulcerative colitis) 7. Known myasthenia gravis 8. Glaucoma 9. Febrile at triage 10. History of head trauma in the past 7 days 11. Presence of any known active infection (eg. on antibiotics or antivirals, diagnosed with active infection in the ED, etc) 12. Current secondary headache (as per the treating physician's clinical impression)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Headache Recurrence at 48 Hours | 48 hours | The primary outcome will be headache recurrence 48 hours after discharge from the ED. Headache recurrence will be defined as: for patients who were pain-free at ED discharge (ie. pain intensity of 0), any return of head pain (ie. pain intensity of 1 or greater) will be coded as a recurrence, and for patients who had persistent head pain at discharge, an increase in head pain since ED discharge will be coded as recurrence as well (ie. an increase in their score on the 4-point scale as compared to their score at ED discharge). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistent Pain Freedom | 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours) and 48 hours | Persistent pain freedom, defined as the proportion of patients in each group who achieved pain freedom at 2 hours (or at the time of ED discharge if prior to 2 hours) and were free of pain without the use of rescue medication at 48 hours, will be assessed |
| Patient Satisfaction | At the time of discharge from the ED (expected median duration in the ED post-treatment = 3 hours), at 48 hours and at 7 day follow-up | Patient satisfaction will be assessed at the time of discharge from the ED and again at follow-up with the following 5-point Likert scale: 5=very satisfied, 4=satisfied, 3=neutral, 2=unsatisfied, 1=very unsatisfied. Here we report patient satisfaction rates at discharge. |
| Headache Recurrence at 7 Day Follow-up | 7 days | The proportion of patients in each group with recurrence within the 7 days following ED discharge will be assessed. |
| Pain Intensity | Baseline, 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours) and at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours) | Pain intensity will be measured on a 4 point rating scale as recommended by the International Headache Society guidelines: a) 0=none, b) 1=mild, c) 2= moderate, d) 4=severe. It will be assessed at 2 hours post-baseline, or at the time of ED discharge if prior to 2 hours and at the time of ED discharge where this exceeds 2 hours post-intervention. Because all participants were discharged prior to 2 hours, we report the pain intensity at the time of ED discharge. |
| Adverse Events at Discharge | 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days | Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the time of ED discharge. All patients were discharged prior to the 2 hour time point. Adverse events reported at follow-up are reported elsewhere (see below). |
| Adverse Events at 48 Hours Post-discharge | 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days | Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the 48 hour follow-up post-discharge. |
| Adverse Events at 7 Days Post-discharge | 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days | Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the 7 day follow-up post-discharge. |
| Revisits Within 7 Days of Discharge From the ED | 7 days | The number of patients with return ED visits within 7 days of ED discharge will be assessed through chart review. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited between December 2016 and June 2017 from the ED at the Children's Hospital of Eastern Ontario, a tertiary care academic pediatric hospital located in Ottawa, Ontario, Canada.
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone Dexamethasone 0.6mg/kg (maximum 15mg) PO x 1 dose
Dexamethasone: Dexamethasone 0.6mg/kg (maximum 15mg) PO x 1 dose | 6 |
| Placebo Matched oral solution in same volume per kg as dexamethasone
Placebo: Matched oral solution | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Placebo | Total | Dexamethasone |
|---|---|---|---|
| Age, Continuous | 13.6 years STANDARD_DEVIATION 0.9 | 13.0 years STANDARD_DEVIATION 2.6 | 12.6 years STANDARD_DEVIATION 3.4 |
| Baseline Pain Intensity Mild | 0 Participants | 0 Participants | 0 Participants |
| Baseline Pain Intensity Moderate | 1 Participants | 3 Participants | 2 Participants |
| Baseline Pain Intensity None | 0 Participants | 0 Participants | 0 Participants |
| Baseline Pain Intensity Severe | 4 Participants | 8 Participants | 4 Participants |
| CTAS Score Emergent | 0 Participants | 0 Participants | 0 Participants |
| CTAS Score Non-Urgent | 0 Participants | 0 Participants | 0 Participants |
| CTAS Score Resuscitation | 0 Participants | 0 Participants | 0 Participants |
| CTAS Score Semi-Urgent | 1 Participants | 1 Participants | 0 Participants |
| CTAS Score Urgent | 4 Participants | 10 Participants | 6 Participants |
| Headache Frequency (Monthly Frequency in Past 3 Months) | 7.2 Headaches STANDARD_DEVIATION 12.8 | 10.3 Headaches STANDARD_DEVIATION 12.6 | 12.6 Headaches STANDARD_DEVIATION 12.9 |
| How Long Participant Has Had Migraines | 2.0 years STANDARD_DEVIATION 1.6 | 3.6 years STANDARD_DEVIATION 6.8 | 5.1 years STANDARD_DEVIATION 9.9 |
| Migraine Type Migraine with aura | 5 Participants | 9 Participants | 4 Participants |
| Migraine Type Migraine without aura | 0 Participants | 3 Participants | 3 Participants |
| PedMIDAS Score | 16.2 units on a scale STANDARD_DEVIATION 17.8 | 41 units on a scale STANDARD_DEVIATION 83.8 | 58.7 units on a scale STANDARD_DEVIATION 108.5 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 5 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants |
| Use of Treatment at Home No | 0 Participants | 2 Participants | 2 Participants |
| Use of Treatment at Home Yes | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 2 / 6 | 3 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Headache Recurrence at 48 Hours
The primary outcome will be headache recurrence 48 hours after discharge from the ED. Headache recurrence will be defined as: for patients who were pain-free at ED discharge (ie. pain intensity of 0), any return of head pain (ie. pain intensity of 1 or greater) will be coded as a recurrence, and for patients who had persistent head pain at discharge, an increase in head pain since ED discharge will be coded as recurrence as well (ie. an increase in their score on the 4-point scale as compared to their score at ED discharge).
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone | Headache Recurrence at 48 Hours | 1 Participants |
| Placebo | Headache Recurrence at 48 Hours | 1 Participants |
Secondary
Adverse Events at 48 Hours Post-discharge
Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the 48 hour follow-up post-discharge.
Time frame: 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone | Adverse Events at 48 Hours Post-discharge | Worsening headache | 1 Participants |
| Dexamethasone | Adverse Events at 48 Hours Post-discharge | Fever | 0 Participants |
| Dexamethasone | Adverse Events at 48 Hours Post-discharge | Constipation | 1 Participants |
| Dexamethasone | Adverse Events at 48 Hours Post-discharge | No adverse events | 4 Participants |
| Placebo | Adverse Events at 48 Hours Post-discharge | No adverse events | 3 Participants |
| Placebo | Adverse Events at 48 Hours Post-discharge | Worsening headache | 1 Participants |
| Placebo | Adverse Events at 48 Hours Post-discharge | Constipation | 0 Participants |
| Placebo | Adverse Events at 48 Hours Post-discharge | Fever | 1 Participants |
Secondary
Adverse Events at 7 Days Post-discharge
Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the 7 day follow-up post-discharge.
Time frame: 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone | Adverse Events at 7 Days Post-discharge | Paresthesias | 0 Participants |
| Dexamethasone | Adverse Events at 7 Days Post-discharge | Headache recurrence | 0 Participants |
| Dexamethasone | Adverse Events at 7 Days Post-discharge | No adverse events | 6 Participants |
| Placebo | Adverse Events at 7 Days Post-discharge | Paresthesias | 1 Participants |
| Placebo | Adverse Events at 7 Days Post-discharge | Headache recurrence | 1 Participants |
| Placebo | Adverse Events at 7 Days Post-discharge | No adverse events | 3 Participants |
Secondary
Adverse Events at Discharge
Adverse events will be queried at 2 hours (or at the time of ED discharge if prior to 2 hours), at discharge and in the follow-up questionnaires at 48 hours and 7 days. Reported here are the adverse events at the time of ED discharge. All patients were discharged prior to the 2 hour time point. Adverse events reported at follow-up are reported elsewhere (see below).
Time frame: 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours), at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours), 48 hours and 7 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone | Adverse Events at Discharge | No adverse events | 6 Participants |
| Dexamethasone | Adverse Events at Discharge | Adverse events | 0 Participants |
| Placebo | Adverse Events at Discharge | No adverse events | 5 Participants |
| Placebo | Adverse Events at Discharge | Adverse events | 0 Participants |
Secondary
Headache Recurrence at 7 Day Follow-up
The proportion of patients in each group with recurrence within the 7 days following ED discharge will be assessed.
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone | Headache Recurrence at 7 Day Follow-up | 0 Participants |
| Placebo | Headache Recurrence at 7 Day Follow-up | 0 Participants |
Secondary
Pain Intensity
Pain intensity will be measured on a 4 point rating scale as recommended by the International Headache Society guidelines: a) 0=none, b) 1=mild, c) 2= moderate, d) 4=severe. It will be assessed at 2 hours post-baseline, or at the time of ED discharge if prior to 2 hours and at the time of ED discharge where this exceeds 2 hours post-intervention. Because all participants were discharged prior to 2 hours, we report the pain intensity at the time of ED discharge.
Time frame: Baseline, 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours) and at the time of discharge from the Emergency Department (ED) if post-treatment ED duration extends beyond 2 hours (expected median duration = 3 hours)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone | Pain Intensity | None | 2 Participants |
| Dexamethasone | Pain Intensity | Mild | 2 Participants |
| Dexamethasone | Pain Intensity | Moderate | 2 Participants |
| Dexamethasone | Pain Intensity | Severe | 0 Participants |
| Placebo | Pain Intensity | Severe | 0 Participants |
| Placebo | Pain Intensity | None | 1 Participants |
| Placebo | Pain Intensity | Moderate | 2 Participants |
| Placebo | Pain Intensity | Mild | 2 Participants |
Secondary
Patient Satisfaction
Patient satisfaction will be assessed at the time of discharge from the ED and again at follow-up with the following 5-point Likert scale: 5=very satisfied, 4=satisfied, 3=neutral, 2=unsatisfied, 1=very unsatisfied. Here we report patient satisfaction rates at discharge.
Time frame: At the time of discharge from the ED (expected median duration in the ED post-treatment = 3 hours), at 48 hours and at 7 day follow-up
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Dexamethasone | Patient Satisfaction | At 48 hour follow-up | Satisfied | 6 Participants |
| Dexamethasone | Patient Satisfaction | At 7 day follow-up | Dissatisfied | 0 Participants |
| Dexamethasone | Patient Satisfaction | At discharge | Satisfied | 6 Participants |
| Dexamethasone | Patient Satisfaction | At discharge | Dissatisfied | 0 Participants |
| Dexamethasone | Patient Satisfaction | At 48 hour follow-up | Dissatisfied | 0 Participants |
| Dexamethasone | Patient Satisfaction | At 7 day follow-up | Satisfied | 6 Participants |
| Placebo | Patient Satisfaction | At 48 hour follow-up | Dissatisfied | 1 Participants |
| Placebo | Patient Satisfaction | At 48 hour follow-up | Satisfied | 4 Participants |
| Placebo | Patient Satisfaction | At 7 day follow-up | Satisfied | 3 Participants |
| Placebo | Patient Satisfaction | At discharge | Dissatisfied | 1 Participants |
| Placebo | Patient Satisfaction | At 7 day follow-up | Dissatisfied | 2 Participants |
| Placebo | Patient Satisfaction | At discharge | Satisfied | 4 Participants |
Secondary
Persistent Pain Freedom
Persistent pain freedom, defined as the proportion of patients in each group who achieved pain freedom at 2 hours (or at the time of ED discharge if prior to 2 hours) and were free of pain without the use of rescue medication at 48 hours, will be assessed
Time frame: 2 hours post-intervention (or at the time of ED discharge if prior to 2 hours) and 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone | Persistent Pain Freedom | 1 Participants |
| Placebo | Persistent Pain Freedom | 1 Participants |
Secondary
Revisits Within 7 Days of Discharge From the ED
The number of patients with return ED visits within 7 days of ED discharge will be assessed through chart review.
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone | Revisits Within 7 Days of Discharge From the ED | 1 Participants |
| Placebo | Revisits Within 7 Days of Discharge From the ED | 0 Participants |