Valproate Versus Ketorolac Versus Metoclopramide

Phase 4

Completed

Conditions: Acute Migraine

Interventions: Drug: Valproate
Drug: Ketorolac
Drug: Metoclopramide

Registration Number: NCT01267864

Lead Sponsor: Montefiore Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 330

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valproate	Valproate	1gm IV
Ketorolac	Ketorolac	Ketorolac 30mg IV
Metoclopramide	Metoclopramide	Metoclopramide 10mg IVSS

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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