Probable MigrainePhase 4EDMigraine-4NCT01596166
Intravenous Ketorolac and Metoclopramide for Pediatric Migraine in the Emergency Department
A Phase 4 study testing Ketorolac Tromethamine and Metoclopramide in people with Probable Migraine and Migraine With Aura, run by University of Alberta at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Probable Migraine, Migraine With Aura, Migraine Without Aura
- What is being tested?
- Ketorolac Tromethamine and Metoclopramide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2012to Apr 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- A patient is legible to participate in this study if they meet the following criteria:
- Patient is between 6 and 17 years of age inclusive
- Treatment with usual therapy at home or at least one dose of oral ibuprofen or acetaminophen has not provided satisfactory relief
- Intravenous therapy is indicated in the opinion of the treating ED physician
- Patient has a history of migraine as defined by the International Classification of Headache Disorders - 2nd edition (Appendix 1) and meets the following criteria:
- 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.
- 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.
Who cannot join
- A patient is not eligible to participate in the study if any of the following criteria apply:
- Patient has a contraindication to the use of metoclopramide or ketorolac in the opinion of the ED physician
- Patient has a ventriculoperitoneal shunt
- Patient has a fever (temperature > 38.5 oC)
- Patient has meningismus or clinical suspicion of meningitis in the opinion of the ED physician
- Patient has a history of head trauma causing headache in the last 1 week prior to presentation to the ED
- Patient is unable to complete the efficacy assessments (e.g. language barrier)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Stollery Children's Hospital
Edmonton, Alberta, T6G 2C8
About this study
Official title: Efficacy of Combination Therapy With Intravenous Ketorolac and Metoclopramide for Pediatric Migraine Therapy in the Emergency Department
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.
Read the 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
- Being tested
- Ketorolac Tromethamine, Metoclopramide
- Keywords
- migraine, pediatric, childhood, emergency department, ketorolac, metoclopramide, intravenous
- Medical subject headings
- Migraine with Aura, Migraine without Aura, Migraine Disorders, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketorolac TromethamineDrug
Also called Toradol, 74103-07-4
Ketorolac 0.5 mg/kg (max 30 mg) IV
MetoclopramideDrug
Also called Maxeran, Reglan, 364-62-5
Metoclopramide 0.2 mg/kg (max 10 mg) IV
| Study group | Role | What they receive |
|---|---|---|
| Metoclopramide, Ketorolac | Experimental | 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 Receives: Drug: Ketorolac Tromethamine; Drug: Metoclopramide |
| Metoclopramide, Placebo | Placebo comparator | 1. 10 mL/kg IV 0.9% sodium chloride
2. Metoclopramide 0.2 mg/kg (max 10 mg) IV
3. Placebo (normal saline) Receives: Drug: Metoclopramide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean reduction in pain intensity
Measured on Visual Analogue Scale (VAS).
Measured: 2 hours
Secondary outcomes (10)
Pain freedom
VAS=0
Measured: 2 hours
Headache relief - 33
Defined as a 33% reduction on the VAS.
Measured: 2 hours
Headache relief - 50
Defined as a 50% reduction on the VAS
Measured: 2 hours
Presence of nausea
Measured: 2 hours
Presence of vomiting
Measured: 2 hours
Use of rescue medications
Permitted per protocol 60 minutes after start if intravenous infusion.
Measured: 2 hours
Sustained pain-free
No recurrence of headache within 24 hours if pain was completely eliminated (VAS = 0) prior to discharge.
Measured: 25 hours
Sustained headache relief
No increase in headache by 33% on the VAS or 50% on the VAS if headache relief was initially achieved.
Measured: 24 hours
Minimum clinically significant difference
- "I would take the medication again"
- "My headache is a bit better/worse"
- "My headache is a lot better/worse"
Measured: 2 hours
Adverse events
All serious and non-serious adverse events including akathisia and dystonia.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startFeb 2012
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Probable MigraineStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Lawrence P. Richer, MD, MSc, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01596166
- Sponsor's protocol ID
- EDMIGR-004-01
- Acronym
- EDMigraine-4
- Status last verified
- Jan 2015
- First submitted
- 8 May 2012
- Last updated
- 26 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Combination Therapy With Intravenous Ketorolac and Metoclopramide for Pediatric Migraine Therapy in the Emergency Department
- ClinicalTrials.gov ID
- NCT01596166
- Acronym / sponsor ID
- EDMigraine-4 / EDMIGR-004-01
- Conditions
- Probable Migraine, Migraine With Aura, Migraine Without Aura
- Keywords
- migraine, pediatric, childhood, emergency department, ketorolac, metoclopramide, intravenous
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Feb 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoclopramide, Ketorolac | Experimental | Drug: Ketorolac Tromethamine, Drug: Metoclopramide1. 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 |
| Metoclopramide, Placebo | Placebo comparator | Drug: Metoclopramide1. 10 mL/kg IV 0.9% sodium chloride 2. Metoclopramide 0.2 mg/kg (max 10 mg) IV 3. Placebo (normal saline) |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Patient is between 6 and 17 years of age inclusive
- Treatment with usual therapy at home or at least one dose of oral ibuprofen or acetaminophen has not provided satisfactory relief
- Intravenous therapy is indicated in the opinion of the treating ED physician
- Patient has a history of migraine as defined by the International Classification of Headache Disorders - 2nd edition (Appendix 1) and meets the following criteria:
Key exclusion criteria (7 listed)
- A patient is not eligible to participate in the study if any of the following criteria apply:
- Patient has a contraindication to the use of metoclopramide or ketorolac in the opinion of the ED physician
- Patient has a ventriculoperitoneal shunt
- Patient has a fever (temperature > 38.5 oC)
- Patient has meningismus or clinical suspicion of meningitis in the opinion of the ED physician
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketorolac TromethamineAlso: Toradol, 74103-07-4Ketorolac 0.5 mg/kg (max 30 mg) IV | Drug | Metoclopramide, Ketorolac |
| MetoclopramideAlso: Maxeran, Reglan, 364-62-5Metoclopramide 0.2 mg/kg (max 10 mg) IV | Drug | Metoclopramide, Ketorolac, Metoclopramide, Placebo |
Primary outcome
Mean reduction in pain intensity
Time frame: 2 hours
Measured on Visual Analogue Scale (VAS).
10 secondary outcomes
Pain freedom
Time frame: 2 hours
Headache relief - 33
Time frame: 2 hours
Headache relief - 50
Time frame: 2 hours
Presence of nausea
Time frame: 2 hours
Presence of vomiting
Time frame: 2 hours
Use of rescue medications
Time frame: 2 hours
Sustained pain-free
Time frame: 25 hours
Sustained headache relief
Time frame: 24 hours
Minimum clinically significant difference
Time frame: 2 hours
Adverse events
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence P. Richer, MD, MSc principal investigator
University of Alberta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketorolac Tromethamine and Metoclopramide in people with Probable Migraine and Migraine With Aura, run by University of Alberta at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean reduction in pain intensity (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2015.