Intravenous Ketorolac and Metoclopramide for Pediatric Migraine in the Emergency Department

NCT ID: NCT01596166

Last Updated: 2015-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-04-30

Brief Summary

Migraine headaches are a common problem for children. When treatment at home fails, children may benefit from intravenous treatment administered in a hospital setting like the Emergency Department. Most treatments used however have only been tested in adults and the best treatment strategy for children is not always clear. The combination of more than one medication is frequently prescribed in Canadian Emergency Departments. The purpose of this study is to investigate whether the combination of ketorolac (an anti-inflammatory pain medication) and metoclopramide (an anti-nauseant that may also relieve migraine headaches) is better than metoclopramide by itself.

Detailed Description

Migraine headache is a painful condition of recurrent moderate to severe head pain associated with nausea, vomiting, photophobia, and phonophobia. The condition is highly prevalent and a significant community health problem with considerable impact on the health care system. To alleviate the pain and morbidity associated with a migraine attack, drug therapies are often employed including simple analgesics like ibuprofen and migraine-specific medications like sumatriptan. When these treatments fail or in severe, intractable cases, patients and families may present to the Emergency Department (ED).

Ketorolac in combination with metoclopramide or prochlorperazine was the most common multi-drug combination used in 36% of ED presentations for migraine across Canada in our national practice variation study. The scientific rationale for combining a non-selective non-steroidal anti-inflammatory drug (NSAID) with inhibition of both the cyclooxygenase (COX) 1 and 2 isoenzymes with other migraine therapies is enticing; however, no studies have specifically examined the relative efficacy of the practice. Why would the combination of a non-selective NSAID like ketorolac with other migraine therapies improve treatment outcomes? The benefit of multi-target combinations may be relate to the duration of the migraine and the multiple brain areas involved in sustained pain. It has long been recognized that patients who treat their migraine headaches early at the onset have a better response. The underlying mechanism for this phenomenon has now been identified. The initiation of migraine pain requires activation of the trigeminal (5th cranial nerve) nociceptive (pain) system. Activation of these sensory fibers within the arachnoid membrane on the surface of the brain produces the first and most common painful manifestation of migraine - the pulsatile headache. With each heartbeat, minor dilation of the cerebral blood vessels produces stretch and a painful activation of the trigeminal fibers known as peripheral sensitization. The second phase in the maintenance of a migraine attack over several hours is the sensitization of trigeminal pain pathways leading to higher brain centers known as central sensitization. The efficacy of medications like the triptans is greater early in the course of a migraine attack when there is only peripheral sensitization and before the onset of central sensitization. Non-selective NSAIDs like naproxen sodium and ketorolac may be uniquely effective in the reduction of central sensitization in the animal model of migraine and the reduction of migraine pain in adult patients late in the course of a migraine headache.

The population of patients in the ED is uniquely different from outpatients in that most have developed their migraine headache hours or days before presenting. In our practice variation study, the mean duration of the migraine prior to presenting to the ED was 2 days. Including an NSAID when treating a prolonged migraine in the ED may thus increase the therapeutic window and improve outcomes. While many Canadian ED physicians have adopted the practice of combining ketorolac with other migraine therapies, the gold standard assessment of efficacy and safety in a randomized clinical trial has not been applied.

Conditions

Probable Migraine; Migraine With Aura; Migraine Without Aura

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Metoclopramide, Ketorolac

1. 10 mL/kg IV 0.9% sodium chloride

2. Metoclopramide 0.2 mg/kg (max 10 mg) IV

3. Ketorolac 0.5 mg/kg (max 30 mg) IV

Group Type: EXPERIMENTAL

Ketorolac Tromethamine

Intervention Type: DRUG

Ketorolac 0.5 mg/kg (max 30 mg) IV

Metoclopramide

Intervention Type: DRUG

Metoclopramide 0.2 mg/kg (max 10 mg) IV

Metoclopramide, Placebo

1. 10 mL/kg IV 0.9% sodium chloride

2. Metoclopramide 0.2 mg/kg (max 10 mg) IV

3. Placebo (normal saline)

Group Type: PLACEBO_COMPARATOR

Metoclopramide

Intervention Type: DRUG

Metoclopramide 0.2 mg/kg (max 10 mg) IV

Interventions

Ketorolac Tromethamine

Ketorolac 0.5 mg/kg (max 30 mg) IV

Intervention Type: DRUG

Metoclopramide

Metoclopramide 0.2 mg/kg (max 10 mg) IV

Intervention Type: DRUG

Other Intervention Names

Toradol; 74103-07-4; Maxeran; Reglan; 364-62-5

Eligibility Criteria

Inclusion Criteria

A patient is legible to participate in this study if they meet the following criteria:

1. Patient is between 6 and 17 years of age inclusive

2. Treatment with usual therapy at home or at least one dose of oral ibuprofen or acetaminophen has not provided satisfactory relief

3. Intravenous therapy is indicated in the opinion of the treating ED physician

4. Patient has a history of migraine as defined by the International Classification of Headache Disorders - 2nd edition (Appendix 1) and meets the following criteria:

1. During headache, at least 1 of the following: nausea and/or vomiting; two of five symptoms (photophobia, phonophobia, difficulty thinking, lightheadedness, or fatigue). Symptoms may be inferred from patient's behavior.

2. Headache has at least 2 of the following characteristics: bifrontal/bitemporal or unilateral location; pulsating/throbbing quality; moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity. Symptoms may be inferred from patient's behavior.

Exclusion Criteria

A patient is not eligible to participate in the study if any of the following criteria apply:

1. Patient has a contraindication to the use of metoclopramide or ketorolac in the opinion of the ED physician

2. Patient has a ventriculoperitoneal shunt

3. Patient has a fever (temperature > 38.5 oC)

4. Patient has meningismus or clinical suspicion of meningitis in the opinion of the ED physician

5. Patient has a history of head trauma causing headache in the last 1 week prior to presentation to the ED

6. Patient is unable to complete the efficacy assessments (e.g. language barrier)

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence P. Richer, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

Countries

Canada

Other Identifiers

EDMIGR-004-01

Identifier Type: -

Identifier Source: org_study_id