Valproate Versus Ketorolac Versus Metoclopramide

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.

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