Valproate Versus Ketorolac Versus Metoclopramide

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Migraine
• Intervention / Treatment: Drug: Metoclopramide; Drug: Ketorolac; Drug: Valproate

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.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metoclopramide; Metoclopramide 10mg IVSS	Drug: Metoclopramide; 10mg IVSS
Active Comparator: Ketorolac; Ketorolac 30mg IV	Drug: Ketorolac; 30g IVSS
Active Comparator: Valproate; 1gm IV	Drug: Valproate; 1gm IVSS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 28, 2010
• First Posted (Estimate): December 29, 2010

Study Record Updates

• Last Update Posted (Actual): June 4, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: metoclopramide; emergency; migraine; ketorolac; valproate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; GABA Agents; Anticonvulsants; Antimanic Agents; Ketorolac; Valproic Acid; Metoclopramide
• Other Study ID Numbers: 10-01-009