Valproate Versus Ketorolac Versus Metoclopramide

Study Overview
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Brief Summary
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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
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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.

Official Title
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IV Valproate for Acute Migraine. A Randomized Comparison Versus IV Metoclopramide and IV Ketorolac

Conditions
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Acute Migraine

Intervention / Treatment
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* Drug: Metoclopramide
* Drug: Ketorolac
* Drug: Valproate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metoclopramide<br>Metoclopramide 10mg IVSS | Drug: Metoclopramide<br>* 10mg IVSS<br>|
| Active Comparator: Ketorolac<br>Ketorolac 30mg IV | Drug: Ketorolac<br>* 30g IVSS<br>|
| Active Comparator: Valproate<br>1gm IV | Drug: Valproate<br>* 1gm IVSS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 60 minutes after receipt of medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2- 24 hours after receipt of medication | 
| 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 | 24 hours | 
| Adverse Event | % who report any adverse event after administration of investigational medication | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine, emergency, metoclopramide, ketorolac, valproate