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Trial registered on ANZCTR


Registration number
ACTRN12615000910505
Ethics application status
Approved
Date submitted
3/08/2015
Date registered
1/09/2015
Date last updated
9/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized controlled trial of propofol versus placebo for the Emergency Department treatment of acute migraine in adults.
Scientific title
In patients presenting to the Emergency Department with acute migraine, is propofol more effective than placebo for headache resolution by one hour.
Secondary ID [1] 287206 0
Nil
Universal Trial Number (UTN)
U1111-1172-8492
Trial acronym
None.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute migraine. 295798 0
Condition category
Condition code
Neurological 296064 296064 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Propofol 200mg/20ml. The 200mg will be drawn up in to a 20ml syringe, the concentration being 10mg/ml. It will be administered in up to 6 intravenous boluses, with the initial bolus being 4 ml (40mg) and subsequent boluses being 2 ml (20mg), so that the maximum dosage will be 14 ml (140mg). Boluses will be administered 3 - 5 minutes apart depending on patient response, with administration ceasing if the headache is resolved (pain rating zero), if an unexpected adverse event occurs, or when the maximum dose is reached. The amount given, and times of administration will be recorded.
Intervention code [1] 292490 0
Treatment: Drugs
Comparator / control treatment
Placebo used will be Intralipid 20%. This is identical in appearance to Propofol and is available in 500ml bags. 20ml will be drawn up in to a 20 ml syringe. It will be administered in the same bolus amounts over the same time periods as described for propofol and will cease when either the headache resolves or the maximum of 14 ml has been given.
Control group
Placebo

Outcomes
Primary outcome [1] 295738 0
% with headache resolution (pain score 0 on the Numerical Rating Scale) by one hour from initial treatment.
Timepoint [1] 295738 0
One hour from intial treatment.
Secondary outcome [1] 316363 0
% with significant reduction in headache (by two or more points on the 0 - 10 numerical rating scale)
Timepoint [1] 316363 0
One hour from initial treatment.
Secondary outcome [2] 316364 0
% with mild residual headache only (1 or 2 on the 0 to 10 numerical rating scale)
Timepoint [2] 316364 0
One hour from initial treatment.
Secondary outcome [3] 316365 0
% requiring additional analgesic medication for migraine. If the pain rating is not zero at one hour, additional medication will be offered as per a defined Rescue Medication Sheet, which sets out the usual current treatments depending on whether the residual headache is mild, moderate or severe. Details of medication given, and response to this (using the numerical pain rating scale 0 - 10), will be recorded on the Rescue Medication Sheet.
Timepoint [3] 316365 0
One hour from initial treatment.
Secondary outcome [4] 316366 0
% reporting that treatment had the desired effect for them, taken as the response to the question:
Did the medication have the desired effect? Yes No
Timepoint [4] 316366 0
One hour from initial treatment.
Secondary outcome [5] 316367 0
% with continued migraine resolution post-discharge. This will be asked on telephone interview and will utilize the numerical rating scale (0 to 10).
Timepoint [5] 316367 0
48 hours post-discharge from the Emergency Department.
Secondary outcome [6] 316368 0
% with adverse events. The most common is stinging at the intravenous injection site. Drowsiness, transient hypotension and transient hypoxaemia are all possible with propofol, but not expected with the low dose boluses being used in this study. Allergic reactions to either preparation, usually to the egg or soy products contained in the emulsion of both preparations are rare (less than 1 per 1000). Presence of abnormal vital signs will be noted during drug administration, as will occurrence of stinging at the injection site. Allergic reaction would also be noted at the time. Given the short half-life of propofol, no adverse reactions related to propofol would be expected after discharge, but patients will be asked to report any symptoms they have at the follow-up phone call.
Timepoint [6] 316368 0
Any time from initial treatment to 48 hours post-discharge.

Eligibility
Key inclusion criteria
Acute migraine, 18 to 65 years of age, patient reported pain on arrival of severity of 4 or more on the 1 to 10 numerical rating scale.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any doubt about diagnosis of migraine for any reason, any associated head injury, any known intracranial pathology, systolic blood pressure less than100 mmHg, use of defined drugs in previous 4 hours (opioids, ergotamine, triptans, neuroleptics or antemetics other than ondansetron), known allergy to propofol, intralipid, egg or soy products. Migraine WITH aura comprising of neurological symptoms, aura being defined as: at least 2 of these, fully reversible aura symptoms: visual symptoms (flickering lights/spots/lines/visual loss) or Sensory symptoms (pins/needles/numbness), or Dysphasic speech disturbance; And at least 2 of these: Homonymous visual and/or unilateral sensory symptoms or at least one aura symptom developing over > 5 min, or Aura symptom(s) lasting between 5 and 60 minutes

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following eligibility check and informed consent, next allocation will be obtained from numbered opaque envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Propofol and Intralipid are of identical milky-white appearance, with the latter (a nutritional supplement) having no known analgesic properties.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Comparison of % with headache resolution by one hour between the two groups (chi square). Past drug versus placebo trials suggest that the highest placebo response for acute migraine is about 40%. Observational studies suggest that propofol may give headache resolution in 80%. Given these results, a sample of 30 per group is sufficient to demonstrate a difference (alpha 0.05, beta 0.9).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4128 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 4129 0
Dandenong Hospital - Dandenong
Recruitment hospital [3] 4130 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 10054 0
3168 - Clayton
Recruitment postcode(s) [2] 10055 0
3175 - Dandenong
Recruitment postcode(s) [3] 10056 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 291776 0
Hospital
Name [1] 291776 0
Dandenong Hospital
Address [1] 291776 0
Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175
Country [1] 291776 0
Australia
Primary sponsor type
Hospital
Name
Dandenong Hospital
Address
Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175
Country
Australia
Secondary sponsor category [1] 290442 0
None
Name [1] 290442 0
Address [1] 290442 0
Country [1] 290442 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293293 0
Monash HREC
Ethics committee address [1] 293293 0
Monash Research Directorate
Monash Medical Centre
246 Clayton Road
Clayton
Victoria
3168
Ethics committee country [1] 293293 0
Australia
Date submitted for ethics approval [1] 293293 0
26/08/2015
Approval date [1] 293293 0
17/11/2015
Ethics approval number [1] 293293 0
15407A

Summary
Brief summary
Acute migraine is a common and often debilitating condition for which people often seek treatment in Emergency Departments. A number of treatments have proven efficacy compared with placebo, including metoclopramide, prochlorperazine, chlorpromazine and sumatriptan. These drugs are reported to lead to headache resolution by 2 hours from initial treatment in about 60% of people. Recent observational studies have suggested that propofol, a sedative and anaesthetic agent, may lead to headache resolution (migraine and tension type headache) by one hour from initial treatment in about 80% of people. These studies have used regimens where incremental small doses of propofol (20 to 40mg) are given every 3 - 5 minutes until either the headache resolves, or a maximum dose of about 140mg has been given. The mechanism of action remains unclear. No studies to date have compared propofol with placebo in adults with acute migraine, which is important, since the placebo response has been reported in previous migraine trials to be up to 40% (although it is most often around 10%). If this study does demonstrate that propofol is significantly superior to placebo, then studies directly comparing propofol with other agents will be warranted.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59278 0
A/Prof Robert Meek
Address 59278 0
Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175
Country 59278 0
Australia
Phone 59278 0
+61 3 95548475
Fax 59278 0
Email 59278 0
robert.meek@monashhealth.org
Contact person for public queries
Name 59279 0
A/Prof Robert Meek
Address 59279 0
Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175
Country 59279 0
Australia
Phone 59279 0
+61 3 95548475
Fax 59279 0
Email 59279 0
robert.meek@monashhealth.org
Contact person for scientific queries
Name 59280 0
A/Prof Robert Meek
Address 59280 0
Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175
Country 59280 0
Australia
Phone 59280 0
+61 3 95548475
Fax 59280 0
Email 59280 0
robert.meek@monashhealth.org

No information has been provided regarding IPD availability
Summary results
No Results