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Trial registered on ANZCTR

Registration number

ACTRN12619001595101

Ethics application status

Approved

Date submitted

4/11/2019

Date registered

19/11/2019

Date last updated

19/11/2019

Date data sharing statement initially provided

19/11/2019

Type of registration

Retrospectively registered

Titles & IDs

Public title

Propofol for Migraine Treatment in Emergency Department

Scientific title

Propofol for Migraine Treatment in Emergency Department
A pilot study, randomised controlled trial, to determine the length of stay in Emergency Department using IV Propofol versus Standard of Care Treatment for acute migraine patients

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

ProMTED

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Migraine

Condition category

Condition code

Anaesthesiology

Pain management

Emergency medicine

Other emergency care

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

What: Intravenous Propofol infusion
- Maximum of 1mg/kg and will be stopped short if the desired effect is achieved with a smaller dose
- Slow infusion over 1 minute
- Intravenous Infusion

Why: A series of small studies and case reports have shown rapid relief of both chronic and acute migraine headache using Propofol, a lipid soluble short-acting intravenous anaesthetic. It seems that the therapeutic effects of Propofol are due to its agonistic effects on the chloride channels in the ß1 subunit of GABA receptors, in addition to its inhibition of afferent sympathetic action and cardiac baroreceptor reflexes. As a result, propofol’s anaesthetic effects on the central nervous system may diminish the central sensitisation causing allodynia and hyperalgesia, (key steps in the pathophysiological development of migraine) attributing to its mechanism of pain relief in migraine patients. Additionally, when Propofol has been safely administered at a sedative dosing, in migraine patients presenting to emergency department (in a case series) has shown rapid pain relief as well as a considerably reduced Length of Stay (LOS) in emergency department.

Who: Migraine patients assessed as meeting the inclusion criteria, with no exclusion criteria, will be consented by site investigator or designee for the patient’s participation in the study. Patients may be administered with 1000ml of normal saline if the treating clinician is concerned about the patient’s hydration level. All enrolled patients will be randomised to receive either the test or the control treatment. The site investigator must follow the appropriate hospital protocols for procedural sedation and treat with up to 1mg/kg intravenous Propofol. Patients receiving Propofol therapy will be transferred to the resuscitation bay with one:one nursing care during the sedation, as is standard practice for all procedural sedations performed in the emergency departments.

How: The drug will be administered as a slow infusion over 1 minute through a peripheral intravenous line with a 10 mL syringe until the patient falls asleep without a rise in end-tidal CO2 or a decrease in respiratory rate or oxygen saturation. The maximum dose of Propofol allowed is 1 mg/kg and will be stopped short if the desired effect is achieved with a smaller dose.

Where: Patients receiving Propofol therapy will be transferred to the resuscitation bay, placed on a cardiac monitor, provided supplemental oxygen by nasal cannula, end-tidal CO2 monitor, with one:one nursing care during the sedation, as is standard practice for all procedural sedations performed in the emergency departments.

When and how much: The drug will be administered as a slow infusion over 1 minute through a peripheral intravenous line with a 10 mL syringe until the patient fell asleep without a rise in end-tidal CO2 or a decrease in respiratory rate or oxygen saturation. The maximum dose of Propofol allowed is 1 mg/kg and will be stopped short if the desired effect is achieved with a smaller dose. The patients will be allowed to sleep until they wake up on his or her own. After the patient is arousable, and patient’s condition must be monitored.

Tailoring: Patients may be administered with 1000ml of normal saline if the treating clinician is concerned about the patient’s hydration level. In the unlikely event that The Alfred Hospital is of the opinion that any aspect of the study protocol creates an immediate hazard to a trial patient, he or she may implement a deviation from or change to the protocol without prior approval from the Alfred Health Human Ethics Committee.
The implemented deviation or change must be reported in a protocol deviation form and reported to the site principal investigator and Alfred Health Human Ethics Committee.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Standard of Care treatment as per Alfred Health Guideline - "Migraine Management"
- Chlorpromazine: 25mg in 1000 mls normal saline IV over 30-60 mins (repeated if necessary), or
- Prochlorperazine 12.5mg intravenous,
- Metoclopramide 10mg intravenous or
- Sumitriptan 6mg sub-cutaneous

Why: Standard of Care (Soc) treatment will be used as the control group for this study. This regime is best practice as per Alfred Health guidelines for patients with migraine in the emergency department.

What: Phenothiazines or Triptans as per the treating clinician. The guideline for SoC has been adapted from Alfred Health Guidelines - "Migraine Management".

Who provided: SoC treatment will be conducted as per treating clinician.

How: Patients will receive SoC face to face via treating clinician. Administration of SoC is via intravenous (IV) infusion, subcutaneous injection or intranasal therapy as follows. - Chlorpromazine: 25mg in 1000 mls normal saline intravenously over 30-60 mins (repeated if necessary), Prochlorperazine 12.5mg intravenously, Metoclopramide 10mg IV + 900 mg soluble aspirin (unless contraindicated + 1L Sodium Chloride 0.9% IV over 2 hours (unless contraindicated),
Sumitriptan 6mg subcutaneously, Sumatriptan 20mg intranasal.
Dosage and therapy as per treating clinician.

Where: All patients in the control group will be treated in the emergency department. If improvement within a suitable timeframe is achieved follow up and discharge will be arranged, if improvement is not achieved within a suitable timeframe admission to neurology will be considered as per SoC.

When/how much/tailoring: Patients will receive SoC as per treating clinician. Variations within the scope of SoC r.e. dosage and administration may be made as per clinicians clinical judgement. All other required data such as the triage waiting and discharge times and duration of sedation, dosage levels and any potential adverse events must be completed by the study investigator or a study-trained research coordinator

Control group

Active

Outcomes

Primary outcome [1]

To determine whether there is any difference in Length of Stay (LoS) in the Emergency Department following an intravenous Propofol regimen and a standard of care regimen, in the treatment of acute migraine headaches among adults presenting to an Emergency Department, Length of stay will be recorded as time of intravenous administration and time of discharge. These times will be determined via review of medical records.

Timepoint [1]

Discharge from the Emergency department

Secondary outcome [1]

To establish whether there is any difference in safety of an intravenous Propofol regimen and a standard of care regimen, in the treatment of acute migraine headaches in adults visiting ED. Safety will be determined by examining for adverse outcomes e.g. desaturation.

Timepoint [1]

Discharge from the Emergency Department

Secondary outcome [2]

To establish whether there is any difference in efficacy of an intravenous Propofol regimen and a standard of care regimen, in the treatment of acute migraine headaches in adults visiting ED. Efficacy will be assessed using pain scores. Patients will be asked to indicate the level of their pain on a 10 cm non-hatched visual analogue pain scale, marked from “0” at one end to “10” at the other. Patients will be verbally instructed that “0” means “no pain” and “10” means the worst pain ever.

Timepoint [2]

Discharge from the Emergency Department

Eligibility

Key inclusion criteria

1. Adult patients (age = 18 to 65 years);
2. Diagnosis of Migraine by the treating clinician
3. Decision to commence intravenous therapy

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Patients with fever, altered mental status or impairment of conscious state
2. Allergy to any of study drugs, eggs or soy products
3. Presence of abnormal neurological signs or suspicion of alternate diagnosis
4. History of head trauma
5. Failure to provide informed consent
6. Inability to mark a visual analogue pain scale (VAS)
7. Nursing home residents; and
8. Pregnancy

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)

Allocation concealment achieved via study specific trial packs containing an ampoule of Propofol or the SOC drug ampoule,

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Study specific trial packs (ProMTED packs) will be randomised as per the computer-generated sequence using a pseudo-random number generator and a 1:1 allocation ratio,

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

This study is a proof-of-concept, pilot study to test the feasibility of a multicenter randomized controlled trial. Therefore, it is not powered to detect a superiority of the IV Propofol for shortening ED LOS.

For safety analysis, all adverse events will be summarised by each AE category. All adverse events reported during or after treatment will be summarised for both IV Propofol and SOC groups by body/organ system, and expressed as an incidence percentage.
All clinically relevant baseline variables will be tabulated. Categorical variables, including binary variables, will be reported by giving the number and percentage of patients in each category. Continuous variables will be reported by presenting the mean, standard deviation, median, minimum and maximum values for each. A comparability analysis of baseline variables between subjects in the test and control groups will be conducted. All baseline variables will be analysed as is, no imputation of missing data will be made. Nevertheless, missing data in the baseline variables are expected to be very limited.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

1/06/2018

Date of last participant enrolment

Anticipated

31/12/2020

Actual

Date of last data collection

Anticipated

31/12/2020

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Melbourne

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

The Alfred

Address [1]

55 Commercial Rd, Melbourne VIC 3004

Country [1]

Australia

Primary sponsor type

Hospital

Name

Emergency & Trauma Centre, The Alfred Hospital

Address

55 Commercial Rd, Melbourne VIC 3004

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Alfred Hospital Ethics Committee

Ethics committee address [1]

55 Commercial Rd, Melbourne VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/07/2016

Approval date [1]

19/08/2016

Ethics approval number [1]

328/16

Summary

Brief summary

The commonly used agents for treatment of migraines in the emergency department (ED) setting are chlorpromazine, prochlorperazine and sumitriptan, with variable success (up to 70% efficacy in several studies). A series of small studies and case reports have shown rapid relief of both chronic and acute migraine headache using Propofol, a lipid soluble short-acting intravenous anaesthetic.  This study aims to determine whether the administration of intravenous (IV) Propofol at a procedural sedative dose (up to 1mg/kg) is associated with shorter length of stay compared to the standard therapy (IV Chlorpromazine or Prochlorperazine or Metoclopramide or SC Sumitriptan) for migraine relief, in an ED setting.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Biswadev Mitra

Address

The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 3 9076 2782

Fax

[email protected]

Contact person for public queries

Name

Biswadev Mitra

Address

The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 3 9076 2782

Fax

[email protected]

Contact person for scientific queries

Name

Biswadev Mitra

Address

The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 3 9076 2782

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Individual patient data will not be made available to protect patient confidentiality.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
5542	Study protocol					378662-(Uploaded-04-11-2019-18-02-31)-Study-related document.pdf
5545	Ethical approval					378662-(Uploaded-04-11-2019-18-03-00)-Study-related document.pdf

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	Propofol for migraine in the emergency department: A pilot randomised controlled trial.	2020	https://dx.doi.org/10.1111/1742-6723.13542

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

Trial Review

Documents added manually

Documents added automatically