Acute Migraine
Conditions
Keywords
migraine, emergency, metoclopramide, ketorolac, valproate
Brief summary
This randomized study is testing 3 different intravenous medications to see which one is best for acute migraine. The three medications are metoclopramide, valproate, and ketorolac.
Detailed description
One million patients present to US emergency departments (ED) annually for treatment of acute migraine headache. A variety of parenteral medications are used to treat acute migraine, but none offer rapid and complete headache relief without side effects. Preliminary studies have suggested that intravenous valproate, an anti-epileptic medication with established efficacy as a migraine preventive, may be useful for the treatment of acute migraine. We propose a randomized, comparative efficacy trial in which intravenous valproate is compared to two standard parenteral therapies for acute migraine. There will not be a placebo control. Included subjects will be adults 64 years and younger who meet International Headache Society criteria for acute migraine, who do not have clinical evidence of secondary (organic) headache, and who do not have allergy or contra-indication to the investigational medications. The investigational medications are 1gm of valproate, 10mg of metoclopramide, and 30mg of ketorolac. Patients will be approached for participation and randomized at the time of presentation to the ED. Pain will be assessed on an 11 point (0 to 10) verbal pain scale, validated for use in acute pain trials. Medication will be infused as a slow intravenous drip. The primary outcome will be an improvement in headache intensity one hour after initiation of the intravenous drip. Secondary outcomes include assessments of pain, functional disability, adverse events, and satisfaction with the investigational medication one, two and 24 hours after initiation of the intravenous drip. The primary analysis will use a Student's t-test for independent samples and involve three pair-wise comparisons. Using an alpha of .017 (to account for the three pairwise comparisons), a standard beta, and a validated minimum clinically significant difference on the verbal pain scale, we calculated the need for 330 subjects. An interim analysis will be conducted to determine lack of efficacy of valproate.
Interventions
DRUGMetoclopramide
10mg IVSS
DRUGKetorolac
30g IVSS
DRUGValproate
1gm IVSS
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
* IHS migraine without aura * IHS probable migraine (all migraine without arua criteria must be met except duration may be \>72 hours or \<4 hours)
Exclusion criteria
* Allergy or contra-indication to investigational medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Headache Pain Level on a 0-10 Verbal Scale | 60 minutes after receipt of medication | Verbal Numerical Rating scale for pain. Absolute change from baseline. This is a 0-10 scale on which 0= no pain and 10= the worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieve Sustained Headache Freedom for 24 Hours | 2- 24 hours after receipt of medication | Number of participants achieving a pain free state within two hours and maintaining the pain free state for 24 hours after receipt of medication |
| Satisfaction With Medication | 24 hours | % who answer the following question affirmatively at 24 hours: Do you want to receive the same medication the next time you present to an ER with an acute migraine |
| Adverse Event | 24 hours | % who report any adverse event after administration of investigational medication |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metoclopramide Metoclopramide 10mg IVSS
Metoclorpamide: 10mg IVSS | 110 |
| Ketorolac Ketorolac 30mg IV
Ketorolac: 30g IVSS | 110 |
| Valproate 1gm IV
Valproate: 1gm IVSS | 110 |
| Total | 330 |
Baseline characteristics
| Characteristic | Metoclopramide | Ketorolac | Valproate | Total |
|---|---|---|---|---|
| Age, Continuous | 34 years | 34 years | 33 years | 33 years |
| Sex: Female, Male Female | 92 Participants | 93 Participants | 91 Participants | 276 Participants |
| Sex: Female, Male Male | 18 Participants | 17 Participants | 19 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 109 | 33 / 110 | 25 / 110 |
| serious Total, serious adverse events | 0 / 109 | 0 / 110 | 0 / 110 |
Outcome results
Primary
Headache Pain Level on a 0-10 Verbal Scale
Verbal Numerical Rating scale for pain. Absolute change from baseline. This is a 0-10 scale on which 0= no pain and 10= the worst pain imaginable.
Time frame: 60 minutes after receipt of medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metoclopramide | Headache Pain Level on a 0-10 Verbal Scale | 4.7 units on a scale |
| Ketorolac | Headache Pain Level on a 0-10 Verbal Scale | 3.9 units on a scale |
| Valproate | Headache Pain Level on a 0-10 Verbal Scale | 2.8 units on a scale |
Secondary
Adverse Event
% who report any adverse event after administration of investigational medication
Time frame: 24 hours
Population: Any adverse event reported at any assessment throughout the study period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metoclopramide | Adverse Event | 24 Participants |
| Ketorolac | Adverse Event | 33 Participants |
| Valproate | Adverse Event | 25 Participants |
Secondary
Participants Who Achieve Sustained Headache Freedom for 24 Hours
Number of participants achieving a pain free state within two hours and maintaining the pain free state for 24 hours after receipt of medication
Time frame: 2- 24 hours after receipt of medication
Population: Please note that 1 patient in the metoclopramide arm and 1 patient in the ketorolac arm were lost-to-follow-up and did not provide data for this outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metoclopramide | Participants Who Achieve Sustained Headache Freedom for 24 Hours | 12 Participants |
| Ketorolac | Participants Who Achieve Sustained Headache Freedom for 24 Hours | 17 Participants |
| Valproate | Participants Who Achieve Sustained Headache Freedom for 24 Hours | 4 Participants |
Secondary
Satisfaction With Medication
% who answer the following question affirmatively at 24 hours: Do you want to receive the same medication the next time you present to an ER with an acute migraine
Time frame: 24 hours
Population: Study participants were telephoned 24 hours after medication administration. 3 patients in the metoclopramide arm, 4 in the ketorolac arm, and 3 in the valproate arm were lost to follow-up and did not provide these data. Additionally, 1 patient in the ketorolac arm did not provide an answer to this question
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metoclopramide | Satisfaction With Medication | 65 Participants |
| Ketorolac | Satisfaction With Medication | 42 Participants |
| Valproate | Satisfaction With Medication | 28 Participants |