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Trial registered on ANZCTR


Registration number
ACTRN12619001083189
Ethics application status
Approved
Date submitted
19/07/2019
Date registered
6/08/2019
Date last updated
10/08/2022
Date data sharing statement initially provided
6/08/2019
Date results provided
2/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A study comparing the changes in lung function following the use of salbutamol and symbicort in adults with asthma
Scientific title
Bronchodilation following repeated administration of budesonide/formoterol vs salbutamol in adult asthma: A randomised, open-label, cross-over study
Secondary ID [1] 298116 0
None
Universal Trial Number (UTN)
U1111-1229-6923
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 312646 0
Condition category
Condition code
Respiratory 311141 311141 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention drug schedule: Budesonide/formoterol 200µg/6µg per actuation from the Turbuhaler, 1 actuation at 30 minute intervals for 4 doses over 90 minutes, followed by 2 actuations on 3 occasions at 20 minute intervals for 1 hour, followed by 2 actuations at 7 hours.
The total duration of administration will be 7 hours.
The intervention will take place at the Medical Research Institute of New Zealand (MRINZ) facility. 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 minimum washout period of 7 days.
Intervention code [1] 314340 0
Treatment: Drugs
Comparator / control treatment
Salbutamol 100µg per actuation from the MDI (Metered Dose Inhaler) and spacer inhaled in a single maximal breath. 2 actuations at 30 minute intervals for 4 doses over 90 minutes, followed by salbutamol 2.5mg via nebuliser on 3 occasions at 20 minute intervals for 1 hour, followed by salbutamol 2.5mg via nebuliser at 7 hours. Prior to leaving the study site, this group will receive 12 actuations of Budesonide 200µg via Turbuhaler.
Control group
Active

Outcomes
Primary outcome [1] 319923 0
Magnitude of bronchodilation at 180 mins as measured by FEV1
Timepoint [1] 319923 0
180 minutes post-intervention commencement
Secondary outcome [1] 369878 0
Magnitude of bronchodilation over time as measured by FEV1 using Spirometry
Timepoint [1] 369878 0
FEV1 at 30 min intervals for 4 hours, then hourly to 8 hours post-intervention commencement
Secondary outcome [2] 369879 0
Levels of airway inflammation over time as measured by FeNO
Timepoint [2] 369879 0
FeNO at 30 min intervals for 4 hours, then hourly to 8 hours post-intervention commencement
Secondary outcome [3] 369880 0
Relief of breathlessness as measured by the Modified Borg Score
Timepoint [3] 369880 0
At 30 minute intervals for 4 hours, then hourly to 8 hours post-intervention commencement
Secondary outcome [4] 369883 0
Changes in serum potassium following treatment using blood sampling
Timepoint [4] 369883 0
At 0, 3 and 8 hours post-intervention commencement
Secondary outcome [5] 369884 0
To determine changes in blood eosinophil count following treatment using blood sampling
Timepoint [5] 369884 0
At 0, 3 and 8 hours post-intervention commencement
Secondary outcome [6] 369885 0
Changes in heart rate following treatment using an ECG
Timepoint [6] 369885 0
At 0, 3 and 8 hours post-intervention commencement
Secondary outcome [7] 373015 0
Changes in QTc following treatment using an ECG
Timepoint [7] 373015 0
At 0, 3 and 8 hours post-intervention commencement

Eligibility
Key inclusion criteria
Doctor diagnosis of asthma.
Age 16 to 65 years.
SABA monotherapy or SABA with regular ICS therapy, or regular ICS/LABA treatment
FEV1 40 to 70% predicted as per GLI 2012 criteria
Change in FEV1 post 400µg salbutamol via MDI through a spacer >12% increase from baseline, and >200ml
Minimum age
16 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Other significant respiratory disorder
Other significant cardiovascular disorder such as history of arrhythmia including atrial fibrillation and supraventricular tachycardia
Current or recent respiratory tract infection in last 4 weeks
Current use of other asthma medications including LAMAs, theophylline, oral corticosteroids, biologics, sodium cromoglycate or nedocromil sodium
Asthma exacerbation requiring oral steroids in last 6 weeks
Current smoker or smoking history with >10 pack year history
QTCF > 430ms for men and > 450ms for women
Pregnant, or planning a pregnancy, or breast feeding
Allergy to investigational products, including previous adverse effects following administration of similar doses to those used in the study
Current use of beta-blockers
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.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Update
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. A similar statistical method will be utilised for analysing the secondary variables: modified Borg score, heart rate and QTC, blood eosinophil and potassium levels.

Data for FeNO will be analysed on the logarithm transformed scale based on our previous experience with the skew distribution of this variable and that normality assumptions were better met on the logarithm transformed scale, interpreted as the ratio of geometric means.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/08/2019
Actual
18/09/2019
Date of last participant enrolment
Anticipated
9/03/2020
Actual
18/10/2020
Date of last data collection
Anticipated
27/03/2020
Actual
1/11/2020
Sample size
Target
39
Accrual to date
Final
39
Recruitment outside Australia
Country [1] 21447 0
New Zealand
State/province [1] 21447 0
Wellington

Funding & Sponsors
Funding source category [1] 302649 0
Commercial sector/Industry
Name [1] 302649 0
AstraZeneca
Country [1] 302649 0
New Zealand
Primary sponsor type
Other
Name
Medical Research Institute of New Zealand
Address
Medical Research Institute of New Zealand
Level 7, CSB Building,
Wellington Hospital,
Newtown
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 302567 0
None
Name [1] 302567 0
Address [1] 302567 0
Country [1] 302567 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303273 0
Health and Disability Ethics Committees
Ethics committee address [1] 303273 0
Ethics committee country [1] 303273 0
New Zealand
Date submitted for ethics approval [1] 303273 0
15/05/2019
Approval date [1] 303273 0
09/07/2019
Ethics approval number [1] 303273 0
19/NTB/83

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

Contacts
Principal investigator
Name 93090 0
Prof Richard Beasley
Address 93090 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242

Level 7, CSB Building,
Wellington Hospital,
Newtown
Wellington 6021
Country 93090 0
New Zealand
Phone 93090 0
+6448050238
Fax 93090 0
Email 93090 0
[email protected]
Contact person for public queries
Name 93091 0
Richard Beasley
Address 93091 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242

Level 7, CSB Building,
Wellington Hospital,
Newtown
Wellington 6021
Country 93091 0
New Zealand
Phone 93091 0
+6448050238
Fax 93091 0
Email 93091 0
[email protected]
Contact person for scientific queries
Name 93092 0
Richard Beasley
Address 93092 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242

Level 7, CSB Building,
Wellington Hospital,
Newtown
Wellington 6021
Country 93092 0
New Zealand
Phone 93092 0
+6448050238
Fax 93092 0
Email 93092 0
[email protected]

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: [email protected].


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2497Ethical approval    377508-(Uploaded-26-07-2019-06-43-11)-Study-related document.pdf
3278Informed consent form    377508-(Uploaded-18-11-2019-06-32-56)-Study-related document.pdf
3279Study protocol    377508-(Uploaded-18-11-2019-06-34-14)-Study-related document.pdf
5837Statistical analysis plan  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.