Migraine
Conditions
Keywords
migraine, headache, metoclopramide, diphenhydramine
Brief summary
Parenteral diphenhydramine is commonly used as adjuvant therapy for acute migraine despite the fact that data supporting this practice do not exist. The investigators propose a randomized double blind study to test the hypothesis that 50mg of intravenous diphenhydramine, when added to standard migraine therapy, will result in a greater rate of sustained headache relief than standard migraine therapy alone. For this study, standard migraine therapy will be 10mg of intravenous metoclopramide. Sustained headache relief is defined as achieving a headache level of mild or none within two hours and maintaining a level of mild or none for 48 hours. Patients who present to the Montefiore emergency room (Bronx, NY) with an acute migraine will be approached for participation. They will be screened for medication contra-indications and non-migraine etiologies of headache. The study will be randomized. Assignment will be concealed. Participants and researchers will be blinded. Efficacy outcomes and adverse events will be assessed every half hour for two hours in the Emergency Department and by telephone 48 hours after medication administration. A sample size calculation, based on pilot data, revealed the need for 374 participants. An interim analysis will be performed after 200 participants have been enrolled with the goal of assessing for lack of conditional power.
Interventions
DRUGmetoclopramide
10 milligrams, administered intravenously over 15 minutes
DRUGdiphenhydramine
50 milligrams, administered intravenously over 15 minutes
DRUGplacebo
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Acute migraine headache * Present to our emergency room in the Bronx, NY for treatment of migraine headache
Exclusion criteria
* Temperature \> 100.3 F * Pheochromocytoma * Seizure disorder * Parkinson's disease * Use of monoamine oxidase (MAO) inhibitors * Use of anti-rejection transplant medications * Use of potassium supplements * Use of pramlintide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Headache Relief Assessed by Self-evaluation | up to 2 hours in Emergency Department, 48 hours after discharge from Emergency Department | Sustained headache relief is defined as achieving a headache level of mild or none within two hours and maintaining a level of mild or none for 48 hours. Patient self-evaluated pain level is solicited every half hour for two hours in the Emergency Department and then by telephone 48 hours after discharge from emergency department |
Countries
United States
Participant flow
Recruitment details
Protocol anticipated enrollment of around 400 participants, however Data Safety Monitoring Board recommended enrollment cut to approximately half
Participants by arm
| Arm | Count |
|---|---|
| Metoclopramide + Diphenhydramine Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes
metoclopramide: 10 milligrams, administered intravenously over 15 minutes
diphenhydramine: 50 milligrams, administered intravenously over 15 minutes | 104 |
| Metoclopramide + Placebo Metoclopramide 10mg + placebo, administered intravenously over 15 minutes
metoclopramide: 10 milligrams, administered intravenously over 15 minutes
placebo | 104 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 1 |
Baseline characteristics
| Characteristic | Metoclopramide + Diphenhydramine | Metoclopramide + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 11 | 36 years STANDARD_DEVIATION 10 | 35 years STANDARD_DEVIATION 10 |
| Duration of headache Prior to Study | 72 Hours | 48 Hours | 48 Hours |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 104 Participants | 104 Participants | 208 Participants |
| Sex: Female, Male Female | 88 Participants | 92 Participants | 180 Participants |
| Sex: Female, Male Male | 16 Participants | 12 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 0 / 104 |
| other Total, other adverse events | 25 / 104 | 21 / 104 |
| serious Total, serious adverse events | 0 / 104 | 0 / 103 |
Outcome results
Primary
Number of Participants With Sustained Headache Relief Assessed by Self-evaluation
Sustained headache relief is defined as achieving a headache level of mild or none within two hours and maintaining a level of mild or none for 48 hours. Patient self-evaluated pain level is solicited every half hour for two hours in the Emergency Department and then by telephone 48 hours after discharge from emergency department
Time frame: up to 2 hours in Emergency Department, 48 hours after discharge from Emergency Department
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metoclopramide + Diphenhydramine | Number of Participants With Sustained Headache Relief Assessed by Self-evaluation | 40 Participants |
| Metoclopramide + Placebo | Number of Participants With Sustained Headache Relief Assessed by Self-evaluation | 38 Participants |