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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] 299696 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ProMTED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 315049 0
Condition category
Condition code
Anaesthesiology 313379 313379 0 0
Pain management
Emergency medicine 313380 313380 0 0
Other emergency care
Neurological 313381 313381 0 0
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] 315965 0
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] 321865 0
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] 321865 0
Discharge from the Emergency department
Secondary outcome [1] 376524 0
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] 376524 0
Discharge from the Emergency Department
Secondary outcome [2] 376900 0
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] 376900 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
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] 15087 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 28384 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304171 0
Hospital
Name [1] 304171 0
The Alfred
Address [1] 304171 0
55 Commercial Rd, Melbourne VIC 3004
Country [1] 304171 0
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] 304408 0
None
Name [1] 304408 0
Address [1] 304408 0
Country [1] 304408 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304645 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 304645 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 304645 0
Australia
Date submitted for ethics approval [1] 304645 0
25/07/2016
Approval date [1] 304645 0
19/08/2016
Ethics approval number [1] 304645 0
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 97706 0
Prof Biswadev Mitra
Address 97706 0
The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004
Country 97706 0
Australia
Phone 97706 0
+61 3 9076 2782
Fax 97706 0
Email 97706 0
biswadev.mitra@monash.edu
Contact person for public queries
Name 97707 0
Prof Biswadev Mitra
Address 97707 0
The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004
Country 97707 0
Australia
Phone 97707 0
+61 3 9076 2782
Fax 97707 0
Email 97707 0
biswadev.mitra@monash.edu
Contact person for scientific queries
Name 97708 0
Prof Biswadev Mitra
Address 97708 0
The Alfred Centre, 99 Commercial Rd, Melbourne VIC 3004
Country 97708 0
Australia
Phone 97708 0
+61 3 9076 2782
Fax 97708 0
Email 97708 0
biswadev.mitra@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5542 0
Study protocol
Citation [1] 5542 0
Link [1] 5542 0
Email [1] 5542 0
Other [1] 5542 0
Type [2] 5545 0
Ethical approval
Citation [2] 5545 0
Link [2] 5545 0
Email [2] 5545 0
Other [2] 5545 0
Summary results
No Results