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Trial registered on ANZCTR


Registration number
ACTRN12614000847617
Ethics application status
Approved
Date submitted
28/07/2014
Date registered
7/08/2014
Date last updated
20/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Wheeze and Steroids in Preschoolers: Main study
Scientific title
In children aged between 24 and 59 months, presenting to emergency departments with acute preschool wheeze associated with a respiratory tract infection, is oral prednisolone 2mg/kg for 3 days equivalent to placebo in terms of respiratory distress measured at 24 hours by the Preschool Respiratory Assessment Measure (PRAM score).
Secondary ID [1] 284841 0
Nil
Universal Trial Number (UTN)
U1111-1157-1526
Trial acronym
WASP: Main study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preschool wheeze 292234 0
Condition category
Condition code
Respiratory 292571 292571 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2mg/kg oral prednisilone, once daily for 3 days. First dose will be directly observed, adherence to doses 2 and 3 will be via parental report without additional monitoring.
Intervention code [1] 289638 0
Treatment: Drugs
Comparator / control treatment
2mg/kg oral placebo, once daily for 3 days. First dose will be directly observed, adherence to doses 2 and 3 will be via parental report without additional monitoring.
Control group
Placebo

Outcomes
Primary outcome [1] 292432 0
Change in PRAM (Preschool Respiratory Assessment Measure) score from baseline to 24 hours after the first dose of study medication.
Timepoint [1] 292432 0
24 hours
Secondary outcome [1] 308935 0
PRAM score at 4 hours/12 hours and discharge from ED.
Timepoint [1] 308935 0
Discharge/4 hours/12 hours.
Secondary outcome [2] 309746 0
Length of stay in ED - measured by data linkage/chart review.
Timepoint [2] 309746 0
Variable.
Secondary outcome [3] 309747 0
Admission Rate - measured by data linkage/chart review.
Timepoint [3] 309747 0
Variable.
Secondary outcome [4] 309748 0
Length of inpatient stay - measured by data linkage/chart review.
Timepoint [4] 309748 0
Variable.
Secondary outcome [5] 309749 0
Adverse events (infection/behaviour) - measured by chart review and parental report.
Timepoint [5] 309749 0
Up to seven days post intervention.
Secondary outcome [6] 309750 0
Amount of salbutamol given in 48 hours - measured by chart review/parental report.
Timepoint [6] 309750 0
48 hours post first dose.
Secondary outcome [7] 309751 0
Amount of salbutamol given in first 7 days - measured by chart review/parental report.
Timepoint [7] 309751 0
7 days post first dose.
Secondary outcome [8] 309752 0
Time to return to normal activity - measured by parental report via survey.
Timepoint [8] 309752 0
Variable.
Secondary outcome [9] 309753 0
Representation to hospital or general practitioner within 7 days with respiratory distress/illness - measured by parental report via survey/chart review/linkage.
Timepoint [9] 309753 0
7 days post first dose.
Secondary outcome [10] 309754 0
Health Care Costs - measured from data linkage/survey of medication use.
Timepoint [10] 309754 0
7 days post first dose.

Eligibility
Key inclusion criteria
Age 24 to 59 months
Wheeze heard with or without a stethoscope
Presenting with an acute respiratory illness
Minimum age
24 Months
Maximum age
59 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
PRAM score < 3
Unable to be followed up in 18-38 hours
Corticosteroid in last 7 days
Chronic respiratory, neurological or cardiac disease
Contraindication to corticosteroid or allergy to prednisilone
History consistent with foreign body inhalation
Currently severe disease (i.e using life threatening asthma protocol or in resuscitation room)
History of life threatening asthma
Previously randomised in WASP study

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)
All patients who present to the ED with a respiratory illness are potential participants for inclusion in the study. Patients who present with other problems (e.g. a fracture or injury) and have wheeze are not eligible. Inclusion and exclusion criteria are listed in the previous section. In practice, the study form CRF1, “patient eligibility,” will be used to assess if a patient is suitable for the WASP study.

CRF1 will be completed on all patients between 24 and 59 months of age (2 and 4 years of age) who present with a respiratory illness and have wheeze.

If a patient is eligible the family will be approached for consent.

Once consented the treating team will open an opaque sealed envelope (to be opened in sequential order). This envelope will contain a randomisation (study number) which will correspond to a bottle of study intervention medication (prednisolone or placebo). These bottles are exactly the same in presentation and taste.

The bottles are prepared by the study pharmacists using a randomisation key developed by the study statistician utilising the random number generator in Excel (Microsoft corporation).

Families, treating team members and outcome assessers are blinded to study group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study participants will be stratified by site, by the study statistician. The randomisation key developed by the study statistician will utilise Excels random number generator (Microsoft corporation).
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistics

Power and number of participants
The study is powered as an equivalence trial, using the standard deviation found in the pilot for change in PRAM at 24 hours of 2.3, this is consistent with the standard deviation of 2.3 found in previous studies, and allowing for 15% lost to follow-up. 400 children will be required to have 95% power to confirm equivalence of prednisolone to placebo (equivalence limit set at 1, minimum detectable difference in PRAM scores)(alpha=0.05). An equivalence design with high power has been chosen as clinicians widely use prednisolone in children with preschool wheeze, thus if prednisolone is found to be equivalent to placebo, in order to influence practice clinicians will require a high level of certainty.

Data analysis
Data from trial clinical research forms (CRFs) will be entered into a trial database, with appropriate data quality checks. Data will then be extracted into SAS for analysis. Analysis will be intention-to-treat. Continuous data (primary outcome) will be assessed for normality, and transformed if appropriate. Continuous data will be reported as means and 95% confidence intervals (CIs), or medians and inter-quartile range (IQR). Differences between groups will be reported as differences between means (95% CI). Dichotomised data will be reported as incidence rates, with differences between groups reported as odds ratios (95% CI) and corresponding number needed to treat/harm (NNT/NNH).

Sensitivity analysis will assess for any differences at baseline between groups and for the impact of missing data.

A priori sub-group analysis will determine the effect of the study interventions in participants determined to be “salbutamol responsive.” Salbutamol response will be determined as a reduction in PRAM score of =3 following 3x600 mcg salbutamol administered via a spacer, or in the first 1 hour of treatment. This sub-group was determined as being clinically relevant as a previous survey of ED physicians (unpublished data) has suggested that they are more likely to prescribe prednisolone to this sub-group group of preschool wheezers on the basis that response to salbutamol may determine likelihood of the wheeze being closer to asthma in phenotype. Based on pilot data the study will have 80% power (alpha=0.05) to determine the effect in this sub-group. A further a priori sub-group analysis will determine the effect of the study interventions in participants determined to be at higher risk of latter asthma, as measured by the Asthma Predictive Index.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/08/2014
Actual
18/08/2014
Date of last participant enrolment
Anticipated
31/12/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment outside Australia
Country [1] 6165 0
New Zealand
State/province [1] 6165 0

Funding & Sponsors
Funding source category [1] 289453 0
Government body
Name [1] 289453 0
Health Research Council of NZ
Country [1] 289453 0
New Zealand
Primary sponsor type
Hospital
Name
Auckland District Health Board
Address
Park Road
Grafton
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 288361 0
Charities/Societies/Foundations
Name [1] 288361 0
ADHB Charitable Trust (A+ Trust)
Address [1] 288361 0
C/O Auckland District Health Board
Park Road
Grafton
Auckland 1142
Country [1] 288361 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291211 0
Health and Disability Ethics Committees
Ethics committee address [1] 291211 0
Ethics committee country [1] 291211 0
New Zealand
Date submitted for ethics approval [1] 291211 0
28/05/2014
Approval date [1] 291211 0
17/06/2014
Ethics approval number [1] 291211 0
14/NTA/83

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

Contacts
Principal investigator
Name 49346 0
Dr Stuart Dalziel
Address 49346 0
Children's Emergency Department
Starship Children's Hospital
Park Rd
Grafton
Auckland 1142
New-Zealand
Country 49346 0
New Zealand
Phone 49346 0
+ 64 9 3074902
Fax 49346 0
Email 49346 0
sdalziel@adhb.govt.nz
Contact person for public queries
Name 49347 0
Megan Bonisch
Address 49347 0
Children's Emergency Department
Starship Children's Hospital
Park Rd
Grafton
Auckland 1142
New-Zealand
Country 49347 0
New Zealand
Phone 49347 0
+ 64 9 3074902
Fax 49347 0
Email 49347 0
mbonisch@adhb.govt.nz
Contact person for scientific queries
Name 49348 0
Stuart Dalziel
Address 49348 0
Children's Emergency Department
Starship Children's Hospital
Park Rd
Grafton
Auckland 1142
New-Zealand
Country 49348 0
New Zealand
Phone 49348 0
+ 64 9 3074902
Fax 49348 0
Email 49348 0
sdalziel@adhb.govt.nz

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
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