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Trial registered on ANZCTR


Registration number
ACTRN12605000627651
Ethics application status
Approved
Date submitted
13/09/2005
Date registered
11/10/2005
Date last updated
11/10/2005
Type of registration
Retrospectively registered

Titles & IDs
Public title
Acute Asthma Rescue Therapy Study Part 2
Scientific title
What are the comparative effectiveness and adverse effects of high dose ICS and OCS in the treatment of acute mild to moderately severe exacerbations of asthma in adults?
Universal Trial Number (UTN)
Trial acronym
AARTS 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 755 0
Condition category
Condition code
Respiratory 831 831 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Two week reliability check - Measure PEF pre bronchodilator BD.
i) Subject excluded from further participation if electronic PEF diary reveals non-compliance (<80% of expected readings performed) or falsified entries (hand written entires not corresponding to electronic diary recorded entries).
ii) if after 2 weeks inclusion criteria not met but satisfactory compliance, then continue for a further fortnight.
2. Commence study. Subject receives treatment pack (first of 2 in concealed and randomised order). Treatment packs consist of:
a) Maintenance ICS. Exacerbation fluticasone (either real drug or placebo marked as extra preventer in case of exacerbation); OCS tablets (either real or placebo dexamethasone); and Rescue tablets (real prednisolone). Subjects may continue short acting reliever of their choice.
3. Routine management of asthma. During this period symptoms, medication use and PEF to be recorded on wakening three time a week.
4. In the event of PEF deterioration consistent with trial definition of exacerbation, the subject commences their treatment pack after contacting one of the investigators. During the treatment period subjects will be requested to record symptoms, medication use and PEF upon awakening and in the evening prior to taking routine and trial medications.
5. Therapy will consist of
- bronchodilator as required + usual ICS + real high dose ICS + placebo OCS
OR
- bronchodilator as required + usual ICS + placebo high dose ICS + real OCS
6. Subjects will continue on the treatment pack for 7 days. Dexamethasone will be given in a constant non-reducing course of approx. 0.1mg/kg day to a maximum of 12 mg as a once daily dose for 7 days. This equates to a dose of 0.6mg/kg of prednisolone and is the recommended dose from a dose finding study by Webb. Obese subjects (BMI greater than 30) will have their dose adjusted to the weight that would achieve a BMI of 30 (borderline obesity) to avoid excessive dosing due to obesity.
7. Subjects classified as treatment failures or whose PEF falls initially to less than 60% of best will be treated with the rescue (real prednisolone) and/or according to the judgement of the relevant trial respiratory physician.
8. Following either the successfully completed 7 day treatment period or rescue therapy the subject will have a four week wash-out period to avoid carry over effect to the next treatment arm. Subjects will be requested to record symptoms and PEF each morning during the washout period to accurately ascertain timing of late relapses/recurrences. During this period subjects will return to taking the dose of fluticasone used prior to the last back titration before the exacerbation if a back titration was performed within 4 weeks, or the same dose as at exacerbation if the last back titration occurred more than 4 weeks prior to the exacerbation.
9. Following the one month washout period, subjects will then collect the next treatment pack and re-enter maintenance phase. Each subject will be followed for 2 exacerbations.
Intervention code [1] 567 0
Treatment: Drugs
Comparator / control treatment
Control group
Placebo

Outcomes
Primary outcome [1] 1063 0
Primary hypotheses - 1) Null hypothesis: there is no clinically meaningful difference in achieved PEF between the two treatment arms.
Timepoint [1] 1063 0
Primary outcome [2] 1065 0
Primary hypotheses - 2) Null hypothesis: there is no clinically meaningful difference in adverse effects between the two treatment arms.
Timepoint [2] 1065 0
Primary outcome [3] 1067 0
The primary outcome is the achieved PEF after 7 days of therapy or at the time of treatment failure.
Timepoint [3] 1067 0
Primary outcome [4] 1066 0
Primary hypotheses - 2) Alternate hypothesis: there is a clinically meaningful difference in adverse effects between the two treatment arms.
Timepoint [4] 1066 0
Primary outcome [5] 1064 0
Primary hypotheses - 1) Alternate hypothesis: there is a clinically meaningful difference in achieved PEF between the two treatment arms.
Timepoint [5] 1064 0
Secondary outcome [1] 1980 0
Failure rate in each group up to seven days following treatment.
Timepoint [1] 1980 0
Secondary outcome [2] 1981 0
Adverse effects of ICS and OCS
Timepoint [2] 1981 0
Measured at the completion of treatment (7 days or earlier if the treatment is ceased because of treatment failure).

Eligibility
Key inclusion criteria
1) Consenting adults. 2) Physician diagnosed asthma AND eithera) have demonstrated a 15% or greater reversibility in FEV1. The reversibility can be historical in the 12 months prior to enrolment; occur spontaneously; or acutely following bronchodilator; or over time following response to bronchodilator and either ICS or OCS.ORb) Show a diurnal variation in PEF of >=20% [(Highest - Lowest)/highest]3) Assessed as requiring ongoing inhaled steroids (ie cannot have trivial or mild asthma)4) Not exhibit ANY of the exclusion criteria.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Mild asthma where exacerbations with PEF less than 80% of best thought to be unlikely during the course of the study.2) Erroneous recording of PEF or falsified entries during the 4 week reliability check. This will be performed using the Vitalograph 2110 Electronic PEF/FEV1 diary. Potential volunteers will be asked to record symptoms and PEF morning and evening for two weeks using the electronic PEF diaries. Hand recorded PEF will be compared to downloaded actual stored PEF to check for reliability and falsified entries. Volunteers with inaccurate or falsified recordings will be excluded from participation. It is understood that this will shift the study from an effectiveness study toward an efficacy study. However, the researchers consider this absolutely essential to ensure valid data collection as up to 22% of volunteers have been shown to falsify entries. Furthermore, studies looking at compliance indicate that the pattern of compliance with PEF tends to become apparent by 2 weeks of recording.3) Asthma requiring continuous OCS or where other agents such as methotrexate, gold or cyclosporin are being trialed.4) No other study drug or trial participation concurrently.NB patients on long acting beta agonists or leukotriene receptor antagonsits will not be excluded.

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)
A randomised, placebo controlled, double blind, crossover study. Subjects with asthma will receive in a double blind randomised order two forms of treatment for mild to moderately severe attacks of asthma. The pharmacy provides the trial pack using a computerised randomisation code. In this way the investigator, subject and research nurse are not aware of which treatment the subject is receiving.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised randomisation code controlled by pharmacy and not accessible to investigators.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2003
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
94
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 919 0
Charities/Societies/Foundations
Name [1] 919 0
Asthma Foundation of Queensland
Country [1] 919 0
Australia
Primary sponsor type
Government body
Name
Mater Health Services Brisbane Respiratory Medicine Research Department
Address
Country
Australia
Secondary sponsor category [1] 777 0
Commercial sector/Industry
Name [1] 777 0
GlaxoSmithKline Australia Pty Ltd (supplying the placebo and fluticasone inhalers
Address [1] 777 0
Country [1] 777 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2207 0
Mater Misericordiae Health services Brisbane Limited
Ethics committee address [1] 2207 0
Ethics committee country [1] 2207 0
Australia
Date submitted for ethics approval [1] 2207 0
Approval date [1] 2207 0
Ethics approval number [1] 2207 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35952 0
Address 35952 0
Country 35952 0
Phone 35952 0
Fax 35952 0
Email 35952 0
Contact person for public queries
Name 9756 0
Dr Simon Bowler
Address 9756 0
Director of Medicine
Mater Misericordiae Adult Hospital
Level 9
South Brisbane QLD 4101
Country 9756 0
Australia
Phone 9756 0
+61 7 38408111
Fax 9756 0
+61 7 38402402
Email 9756 0
simon. bowler@mater.org.au
Contact person for scientific queries
Name 684 0
Dr Glenn Rice-McDonald
Address 684 0
The Mater Medical Centre
Suite 22 Level 6
293 Vulture Street
South Brisbance QLD 4101
Country 684 0
Australia
Phone 684 0
+61 7 38449176
Fax 684 0
+61 7 38445624
Email 684 0
G.RiceMcDonald@uq.net.au

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

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