ANZCTR - Registration

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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]

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.

Condition category

Condition code

Neurological

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]

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]

% with headache resolution (pain score 0 on the Numerical Rating Scale) by one hour from initial treatment.

Timepoint [1]

One hour from intial treatment.

Secondary outcome [1]

% with significant reduction in headache (by two or more points on the 0 - 10 numerical rating scale)

Timepoint [1]

One hour from initial treatment.

Secondary outcome [2]

% with mild residual headache only (1 or 2 on the 0 to 10 numerical rating scale)

Timepoint [2]

One hour from initial treatment.

Secondary outcome [3]

% 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]

One hour from initial treatment.

Secondary outcome [4]

% 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]

One hour from initial treatment.

Secondary outcome [5]

% 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]

48 hours post-discharge from the Emergency Department.

Secondary outcome [6]

% 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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/10/2015

Actual

1/02/2016

Date of last participant enrolment

Anticipated

31/12/2017

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]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [2]

Dandenong Hospital - Dandenong

Recruitment hospital [3]

Casey Hospital - Berwick

Recruitment postcode(s) [1]

3168 - Clayton

Recruitment postcode(s) [2]

3175 - Dandenong

Recruitment postcode(s) [3]

3806 - Berwick

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Dandenong Hospital

Address [1]

Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash HREC

Ethics committee address [1]

Monash Research Directorate
Monash Medical Centre
246 Clayton Road
Clayton
Victoria
3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/08/2015

Approval date [1]

17/11/2015

Ethics approval number [1]

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

A/Prof Robert Meek

Address

Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175

Country

Australia

Phone

+61 3 95548475

Fax

robert.meek@monashhealth.org

Contact person for public queries

Name

Robert Meek

Address

Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175

Country

Australia

Phone

+61 3 95548475

Fax

robert.meek@monashhealth.org

Contact person for scientific queries

Name

Robert Meek

Address

Emergency Department
Dandenong Hospital
135 David Street
Dandenong
Victoria
3175

Country

Australia

Phone

+61 3 95548475

Fax

robert.meek@monashhealth.org

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Comparing propofol with placebo for early resolution of acute migraine in adult emergency department patients: A double-blind randomised controlled trial.	2021	https://dx.doi.org/10.1111/1742-6723.13659

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically