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Trial registered on ANZCTR


Registration number
ACTRN12619001387112
Ethics application status
Approved
Date submitted
23/09/2019
Date registered
10/10/2019
Date last updated
10/10/2019
Date data sharing statement initially provided
10/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study comparing the speed of airway dilatation following a single dose of salbutamol versus a single dose of symbicort in adult asthmatics
Scientific title
Speed of bronchodilator onset at 2 minutes after a single rescue dose of budesonide/formoterol Turbuhaler vs salbutamol pMDI in adult asthmatics.
Secondary ID [1] 299314 0
Nil
Universal Trial Number (UTN)
U1111-1236-7263
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
asthma 314450 0
Bronchodilation 314451 0
Condition category
Condition code
Respiratory 312785 312785 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention arm: Budesonide/formoterol 200/6mcg, one actuation
Spirometry will be condcuted at baseline, 1,2,3,5,10,15 and 30 minutes post dose.
Visual Analogue Score administered at 1,2,3,5,10,15 and 30 minutes post dose
mBORG Scale administered at baseline and 10 minutes.

Total duration will be approximately 1 hour and will be conducted at the Medical research Institute of New Zealand (MRINZ)

The study drugs will be administered by a study investigator and therefore there is no need to monitor adherence.
An actuation is defined as an 'inhalation or puff from an inhaler'.
Due to the cross over design, there will be a washout period of 7 days
Intervention code [1] 315581 0
Treatment: Drugs
Comparator / control treatment
Comparator arm: Salbutamol 100mcg, 2 actuations.
Intervention arm: Symbicort 200/6mcg 1 actuation
Control group
Active

Outcomes
Primary outcome [1] 321403 0
FEV1 measured by spirometry
Timepoint [1] 321403 0
at 2 minutes
Secondary outcome [1] 374884 0
To determine the time course of bronchodilator effect over 30 minutes measured by spirometry.
Timepoint [1] 374884 0
FEV1 at 1, 2, 3, 5, 10, 15 and 30 minutes.
Secondary outcome [2] 374885 0
To measure perceived bronchodilator effect over 30 minutes.
Timepoint [2] 374885 0
VAS Questionnaire administered at 1, 2, 3, 5, 10, 15 and 30 minutes.
Secondary outcome [3] 375651 0
mBorg questionnaire to measure percieved shortness of breath
Timepoint [3] 375651 0
mBorg administered prior to intervention and again at 10 and 30 minutes post dose

Eligibility
Key inclusion criteria
• Self-reported doctor diagnosis of asthma.
• Age 18 to 65 years at time of consent.
• Allowed asthma treatments are SABA as reliever, regular maintenance ICS therapy together with SABA as a reliever, regular maintenance ICS , LABA with SABA as a reliever or ICS/LABA as a reliever.
• FEV1 greater than 50% predicted using the GLI2012 predicted values at the screening visit.
• Change in FEV1 within 30 minutes of 200mcg salbutamol being administered must be at least 10% and at least 200ml improvement from baseline in FEV1.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Other clinically significant respiratory or cardiovascular disorder.
• Current or recent respiratory tract infection not resolved within the 4 weeks prior to the randomisation visit.
• Current or intermittent use of LTRA therapy, LAMA, SAMA, theophylline, biologics, sodium cromoglycate or nedocromil sodium or non-selective beta blockers within 4 weeks of randomisation.
• Asthma exacerbation requiring oral steroids within the 6 weeks prior to the randomistaion visit.
• Ex-smokers or current smokers with a history >10 pack years.
• Pregnant, or planning a pregnancy, or breast feeding.
• Allergy or contraindication to investigational products.
• Any other condition which, at the investigator’s discretion, is believed may present a safety risk or impact the feasibility of the study or the study results.
• Unable to perform spirometry.
• Unable to use correct inhaler technique at both screening and prior to intervention 1.
• Unable to withhold usual asthma medications prior to screening and each intervention.

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)
Following the screening process, eligible participants who have given written consent to be enrolled in the study will be randomised 1:1 to one of the treatment arms. The allocations will be concealed and a participant’s randomisation outcome will only be released at the time of randomisation. Allocation was by central randomisation done by a computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation method will involve a computer-generated sequence supplied by the study statistician, independent of the investigators. The sequence will be uploaded into the Research Electronic Data Capture (REDCap) system by an individual who is otherwise uninvolved in study processes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome will be FEV1 at 2 minutes. A mixed linear model will be used with the baseline FEV1, treatment allocation, and treatment order as fixed effects; and participant treated as a random effect to take into account the cross-over design. For the FEV1 at other measurement times a time by treatment interaction will be fitted and if statistically significant individual time-wise comparisons will be estimated between treatments.

In a feasibility study the SD for paired FEV1 measurements was about 160mL (at both 2 and 5 minutes).
The non-inferiority bounds were set between plus or minus 60mL equivalent to 25% of the minimal ` perceivable improvement of 230mL9.
The feasibility study was a cross-over design, with a paired t-test assessment for the difference, at 80% power and alpha of 5%, 46 participants are needed based on a paired SD of 160mL. To allow for an 8% dropout rate 50 subjects will be recruited.
Significance of P<0.05 is set for the primary outcome variable.

Recruitment
Recruitment status
Not yet 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 outside Australia
Country [1] 21864 0
New Zealand
State/province [1] 21864 0
Wellington

Funding & Sponsors
Funding source category [1] 303833 0
Other
Name [1] 303833 0
The Medical Research Institute of New Zealand
Address [1] 303833 0
Level 7, CSB, Wellington hospital, Riddiford St, Newtown, Wellington 6021
Country [1] 303833 0
New Zealand
Primary sponsor type
Other
Name
The Medical Research Institute of New Zealand
Address
Level 7, CSB, Wellington hospital, Riddiford St, Newtown, Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 303960 0
None
Name [1] 303960 0
Address [1] 303960 0
Country [1] 303960 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304348 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 304348 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 304348 0
New Zealand
Date submitted for ethics approval [1] 304348 0
29/08/2019
Approval date [1] 304348 0
20/09/2019
Ethics approval number [1] 304348 0
19/STH/170

Summary
Brief summary
Budesonide/formoterol as a reliever has superior efficacy to SABA reliever therapy in adults with mild asthma reducing the number of severe exacerbations, improving asthma control and reducing airway inflammation.

To have confidence in budesonide/formoterol reliever therapy it is necessary to define its onset of action as a bronchodilator as it would be self-administered by patients the community to relieve symptoms.

Patient perception that SABA's relieve symptoms better than budesonide/formoterol could be a barrier to asthmatics confidence of budesonide/formoterol for symptom relief which is an important consideration.
Trial website
Nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96634 0
Prof Richard Beasley
Address 96634 0
MRINZ
Level 7
CSB
Wellington hospital
Riddiford St
Newtown
Wellington
6021
Country 96634 0
New Zealand
Phone 96634 0
+64 48050238
Fax 96634 0
+64 43895707
Email 96634 0
richard.beasley@mrinz.ac.nz
Contact person for public queries
Name 96635 0
Prof Richard Beasley
Address 96635 0
MRINZ
Level 7
CSB
Wellington hospital
Riddiford St
Newtown
Wellington
6021
Country 96635 0
New Zealand
Phone 96635 0
+64 48050238
Fax 96635 0
+64 43895707
Email 96635 0
richard.beasley@mrinz.ac.nz
Contact person for scientific queries
Name 96636 0
Prof Richard Beasley
Address 96636 0
MRINZ
Level 7
CSB
Wellington hospital
Riddiford St
Newtown
Wellington
6021
Country 96636 0
New Zealand
Phone 96636 0
+64 48050238
Fax 96636 0
+64 43895707
Email 96636 0
richard.beasley@mrinz.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after de­ identification (text, tables, figures, and appendices).
When will data be available (start and end dates)?
One year after publication until a minimum of 5 years after publication.
Available to whom?
Researchers who provide a methodologically sound proposal that has been approved by the study steering committee.
Available for what types of analyses?
To achieve the aims outlined in the approved proposal.
How or where can data be obtained?
Through a signed data access agreement. The agreement can be obtained by emailing the Principal Investigator: richard.beasley@mrinz.ac.nz.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 4841 0
Study protocol
Citation [1] 4841 0
Link [1] 4841 0
Email [1] 4841 0
Other [1] 4841 0
file attached
Type [2] 4842 0
Informed consent form
Citation [2] 4842 0
Link [2] 4842 0
Email [2] 4842 0
Other [2] 4842 0
file attached
Type [3] 5028 0
Ethical approval
Citation [3] 5028 0
Link [3] 5028 0
Email [3] 5028 0
Other [3] 5028 0
file attached
Summary results
No Results