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Trial registered on ANZCTR

Registration number

ACTRN12618000138280

Ethics application status

Approved

Date submitted

23/01/2018

Date registered

30/01/2018

Date last updated

22/03/2021

Date data sharing statement initially provided

9/01/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The STELAR trial: Intravenous stemetil versus intravenous largactil for the treatment of acute migraine in adults

Scientific title

The STELAR trial: A prospective, randomised, double-blind trial assessing the effectiveness of intravenous chlorpromazine versus intravenous prochlorperazine on headache severity in the treatment of acute migraine in adults

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

The STELAR trial

Linked study record

Health condition

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

Migraine

Condition category

Condition code

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Arm 1 - Chlorpromazine arm:

12.5 mg chlorpromazine hydrochloride administered in 500 mL sodium chloride 0.9% - given over 30 minutes as an IV infusion. Single dose.

This is a fixed dose for all patients enrolled in the study and randomised to the chlorpromazine arm.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Arm 2 - Prochlorperazine arm:

12.5mg prochlorperazine mesilate administered in 500mL of sodium chloride 0.9% - given over 30 minutes as an IV infusion. Single dose.

This is a fixed dose for all patients enrolled in the study and randomised to the prochlorperazine arm.

Control group

Active

Outcomes

Primary outcome [1]

The change in headache severity on a numerical rating scale (NRS, scale 0-10) at 60 minutes after infusion of either IV chlorpromazine with IV fluid or IV prochlorperazine with IV fluid.

Timepoint [1]

60 minutes post study drug infusion.

Secondary outcome [1]

The change in headache severity on a numerical rating scale at 30 and 120 minutes after infusion of either IV chlorpromazine with IV fluid or IV prochlorperazine with IV fluid.

Timepoint [1]

30 and 120 minutes post study drug infusion.

Secondary outcome [2]

The change in nausea severity on an numerical rating scale (scale 0-10), at 30, 60, and 120 minutes after infusion of either study drug.

Timepoint [2]

30, 60, 120 minutes post study drug infusion.

Secondary outcome [3]

The presence of side effects (e.g., hypotension [systolic BP < 90mmHg, or a change from baseline of > 20mmHg] at 30, 60 and 120 minutes, postural hypotension (an orthostatic drop in systolic BP by > 20mmHg) at the end of the 120 minute period, akathisia (assessed using a modified Prince Henry Hospital Akathisia Rating Scale), and dystonic reactions as assessed by the treating physician.

Timepoint [3]

30, 60 and 120 minutes post infusion of study drug.

Secondary outcome [4]

Percentage of patients from each group requiring rescue therapy (additional medication to manage their symptoms).

Timepoint [4]

60 and 120 minutes post infusion of study drug.

Secondary outcome [5]

The presence of photophobia (yes/no) at 30, 60, and 120 minutes after infusion of either study drug.

Timepoint [5]

30, 60 and 120 minutes

Secondary outcome [6]

The presence of phonophobia (yes/no) at 30, 60, and 120 minutes after infusion of either study drug.

Timepoint [6]

30, 60 and 120 minutes

Eligibility

Key inclusion criteria

Age greater than or equal to 18 or less than or equal to 65 years of age.

Meet Austin Health's acute migraine guidelines for management of adults in the emergency department (ED).

AND:

Meet modified International Classification of Headache Disorders (3rd Edition) - diagnostic criteria for migraine without aura:

1. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
2. Headache has at least two of the following four characteristics:
- Unilateral location
- Pulsating quality
- Moderate or severe pain intensity
- Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)
2. During headache at least one of the following:
- Nausea and vomiting
- Photophobia and phonophobia

3. Not better accounted for by another diagnosis.

These criteria have been modified. The International Classification of Headache Disorders diagnostic criteria requires the patient to have had at least 5 attacks meeting these criteria, we will include any patient in whom this is not the first presentation. We hypothesise that few patients will be able to recall the exact number of migraines they will previously have suffered. This modification has also been used in a previous study to diagnose migraine prior to enrolment.

OR:

Meet International Classification of Headache Disorders (3rd Edition) - diagnostic criteria for migraine with aura:

1. At least two attacks fulfilling criteria A and B
A - One or more of the following fully reversible aura symptoms:
Visual
Sensory
Speech and/or language
Motor
Brainstem
Retinal

B - At least two of the following four characteristics:
- At least one aura symptom spreads gradually over = 5 minutes, and/or two or more symptoms occur in succession
- Each individual aura symptom lasts 5-60 minutes
- At least one aura symptom is unilateral
- The aura is accompanied, or followed within 60 minutes, by headache.

2. Not better accounted for by another diagnosis.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. First headache of this nature.
2. Worst headache they have ever had
3. New onset headache after age 50 years, if not previously investigated.
4. Atypical or unusual character that does not fulfil criteria for migraine.
5. Confusion or loss of consciousness.
6. Seizure.
7. Fever, myalgia, suspicion of meningism or signs of meningism on exam.
8. Abnormal neurological exam.
9. Temporal artery tenderness.
10. Allergy to either study drug.
11. Pregnancy or breastfeeding.
12. Parkinson's Disease.

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 by sealed opaque numbered envelopes.

Pre-randomised by pharmacy department.

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

Simple randomisation using a randomisation table created by computer software.

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

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

The sample size is based upon the primary endpoint i.e. numerical rating pain score at 60 minutes post administration of the study drug.

A minimum sample size of 33 participants in each group is required to demonstrate a difference in pain score of 2 at 60 minutes (expected SD 2.5, alpha 0.05, power 90%). This number has been rounded up to 35 participants in each group (total 70) to account for the estimation of the SD and to afford additional power to the study.

Microsoft Excel 2007 will be used for data storage and interpretation. The unpaired t-test will be employed to analyse the primary endpoint (pain score at 60 minutes) and other continuous variables. The Chi square tests will be employed to compare proportions. IBM SPSS Statistics will be used for statistical analysis.

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

Outbreak of COVID 19

Date of first participant enrolment

Anticipated

1/03/2018

Actual

23/04/2018

Date of last participant enrolment

Anticipated

1/10/2019

Actual

9/03/2020

Date of last data collection

Anticipated

1/10/2019

Actual

9/03/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Health Emergency Department

Address [1]

Emergency Department
Austin Health
Studley Road
Heidelberg
Victoria
3084

Country [1]

Australia

Primary sponsor type

Individual

Name

Sarah Hodgson

Address

Emergency Department
Austin Health
Studley Road
Heidelberg
Victoria
3084

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Shaun Greene

Address [1]

Emergency Department
Austin Health
Studley Road
Heidelberg
Victoria
3084

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research and Ethics Committee

Ethics committee address [1]

Austin Health Human Research and Ethics Committee
Austin Health
Studley Road
Heidelberg
Victoria 
3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

31/01/2018

Approval date [1]

19/04/2018

Ethics approval number [1]

Summary

Brief summary

Lay Summary:

Several intravenous (IV) medications have been shown to be effective in alleviating the symptoms of migraine. At this time we do not know which of these medications is the most effective in patients presenting to hospital with persistent migraine, despite oral therapy. This study aims to compare the two common IV migraine medications used in Australasia: chlorpromazine and prochlorperazine. Our current migraine guideline in the Austin Hospital Emergency Department (ED) states that patients can be given either IV chlorpromazine or IV or intramuscular prochlorperazine for the treatment of migraine. Hence, both treatment regimens are considered as standard practice. Although there is a paucity of evidence available, we hypothesise that IV chlorpromazine is superior to IV prochlorperazine for the management of acute migraine in adults. 
 
Study design: This is a prospective, randomised, double-blind clinical trial comparing the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the management of acute migraine in adults aged 18-65. This will be a single centre study, and will take place at the Austin Hospital.

Method/intervention description: Patients age 18-65 years who present to the Austin ED with migraine, and who meet the criteria in the current Acute migraine guidelines for management of adults in the ED will be considered eligible for assessment to participate in this trial.

Eligible patients will be randomised to receive either:

Chlorpromazine 12.5 mg with 500 mL sodium chloride 0.9% via intravenous infusion over 30 minutes

Or, 

Prochlorperazine 12.5 mg with 500 mL sodium chloride 0.9% via intravenous infusion over 30 minutes.

Patients will be assessed at 0, 30, 60 and 120 minutes post infusion of study drug, Basic observations will be recorded, and headache severity score and nausea severity score using a 11-point numerical rating scale will be recorded. Patients will also be asked if photophobia and phonophobia are present. 

Side effects will be recorded, and at 120 minutes patients will be assessed for postural hypotension, and for akathisia using a modified Prince Henry akathisia rating scale.

At 120 minutes the trial is complete, and if patients symptoms have improved they will be discharged home as per the standard discharge protocol.



Primary objective: To compare the change in headache severity 60 minutes after infusion of either IV chlorpromazine or IV prochlorperazine.

Secondary objectives: 
1. To compare the change in headache severity 30 and 120 minutes after infusion of either study drug.
2. To compare the change in nausea severity, photophobia and phonophobia at 30, 60 and 120 minutes after infusion of either study drug.
3. To compare the side effects of both study drugs.
4. To compare the proportion of patients in each group that require rescue therapy (additional medication to manage their symptoms).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Shaun Greene

Address

Emergency Department
Austin Health
Studley Road
Heidelberg
Victoria
3056

Country

Australia

Phone

+ 61 03 94968409

Fax

[email protected]

Contact person for public queries

Name

Sarah Hodgson

Address

Austin Health
Studley Road
Heidelberg
Victoria
3056

Country

Australia

Phone

+61 03 9496 5000

Fax

[email protected]

Contact person for scientific queries

Name

Sarah Hodgson

Address

Emergency Department
Austin Health
Studley Road
Heidelberg
Victoria
3056

Country

Australia

Phone

+61 0449992471

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

No - individual participant data for this trial will not be available. The only data available will be that published or presented.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
11119	Study protocol			[email protected]

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	A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.	2021	https://dx.doi.org/10.1111/head.14091

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

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