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Trial registered on ANZCTR


Registration number
ACTRN12619001008112p
Ethics application status
Not yet submitted
Date submitted
23/06/2019
Date registered
15/07/2019
Date last updated
15/07/2019
Date data sharing statement initially provided
15/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
BREATH STUDY: Short and long-term effects of therapeutic exercise in children with bronchiectasis: a multi-centre randomised controlled trial
Scientific title
The effectiveness of a therapeutic, play-based exercise program in reducing acute exacerbations over a 12-month period in children aged 6 to less than 13 years with bronchiectasis compared to standard care: a multi-centre, observer-blinded randomised controlled trial
Secondary ID [1] 298575 0
Nil
Universal Trial Number (UTN)
U1111-1233-1961
Trial acronym
BREATH Study
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Bronchiectasis 313416 0
Condition category
Condition code
Respiratory 311851 311851 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A tailored therapeutic exercise programme delivered by trained exercise therapists. The program focuses on developing and enhancing children’s confidence, motivation, functional motor skills (FMS) proficiency, and aerobic fitness through the use of developmentally-appropriate, play-based activity stations designed specifically to suit individual needs. It is comprised of a combination of supervised and unsupervised exercise therapy sessions. Therapists and parents will be required to follow a detailed program manual and standard operating procedures. Sessions will be conducted in local community centres or at the Centre for Children's Health Research South Brisbane.

The supervised component consists of 60-minute group sessions, completed on a weekly basis for 8 weeks, led by a clinical exercise physiologist or physiotherapist. During the supervised group sessions, children rotate through at least 6 activity stations where they complete developmentally appropriate games targeting specific FMS’s. The activity stations are sequenced so that a high intensity game is always followed by a low intensity game, thus ensuring that aerobic fitness is promoted in a safe and effective manner. Activities are tailored to the child’s fitness and skill level by modifying the intensity and duration of each session, and/or modifying the equipment. There will be up to six children each session.

Children will participate in a warm up followed by a circuit of different activities and games targeting functional movement skills and cardiovascular fitness. There will be a group activity at the half way point and the session will end with a cool down. Children spend six minutes at each activity; 30s to switch stations, 30s to orientate to game, 5 minutes to complete activity (chosen from the FMS Activity Catalogue) before moving to the next activity.

Each activity is designed to be tailored to the child’s individual fitness and skill level
One group activity is incorporated per session to target social connection, work as a team and integrate into a bigger group. The group activity will be a modified game from the FMS Activity Catalogue. The group activity is 10 minutes long

Heart rate will be monitored during the session using an upper arm monitor. Data collection will include a subjective rates from the instructor on the effectiveness of the game.

Example outline of an 8-week program -
Weeks
1-8

Warm up- 6 min
FMS Activity - Kicking 6 min
Strength 6 min
Hit, strike, dribble 6 min

Group Activity/Game
10 min FMS Activity
Throwing & Catching 6 min
Balance 6 min
Agility & coordination 6 min
Cool down 2 min


The unsupervised component consists of a home-based, parent-led exercise program, completed 2 days per week (~ 20 minutes per session) for 8 weeks (the same 8 weeks in which the supervised session is taking place), during which children and parents complete 2 games or activity stations from their most recent 60-minute supervised group session. Examples of games targeting a range of FMS’s and fitness parameters, including kicking, underarm striking, throwing and catching, locomotion, strength, and balance. All sessions begin with a 5-minute warm up and end with a 5-minute cool down consisting of stretching and relaxation exercises. Exercise intensity during each program session is monitored continuously with a heart rate monitor. Fidelity is measure via parent report and parent records of heart rate and activities conducted at each session.

Intervention code [1] 314835 0
Treatment: Other
Comparator / control treatment
The control group will receive their usual bronchiectasis care which involves routine specialist clinic reviews every six months and review by general practitioners if required. They will enter a wait-list to receive the intervention once their 12-months of follow-up of usual care has been completed.
Control group
Active

Outcomes
Primary outcome [1] 320523 0
Acute respiratory exacerbations of bronchiectasis assessed by parent report and medical review. An exacerbation is defined as treatment by clinic or hospital staff with antibiotics for any of the following (as recorded in the medical chart or parent report): increased cough (must be wet and of at least 3 days duration), dyspnoea, increased sputum volume or colour intensity, new chest examination or radiographic findings, deterioration in (FEV1) percentage by more than 10%, or haemoptysis.
Timepoint [1] 320523 0
12-months following enrolment
Secondary outcome [1] 371914 0
Health-related quality of life measured using the Peds-QoL questionnaire
Timepoint [1] 371914 0
9 weeks, 6 and 12 months following enrolment.
Secondary outcome [2] 371915 0
Cost-effectiveness of the intervention. This will focus on health resource use and costs as reported in medical records and parent-report at each follow-up time point. Staff administering the intervention will also record associated costs such as time, travel and equipment.
Timepoint [2] 371915 0
12-months following enrolment
Secondary outcome [3] 371916 0
Lung function (measured by forced expiratory volume at 1 second (FEV1)) assessed by routine spirometry at each time point.
Timepoint [3] 371916 0
9 weeks, 6 and 12 months following enrolment
Secondary outcome [4] 371917 0
Aerobic fitness: will be measured using the Modified Shuttle Test (MST). This test requires participants to move back and forth on a 10 m course in time with a sound signal from a pre-recorded tape. Speed for the first minute is set to 1.8 km/hr and increased by 0.61 km/h every minute thereafter. When the participants can no longer follow the pace, the last stage completed is used to predict maximal oxygen uptake (Peak VO2) measured as per SOPs.
Timepoint [4] 371917 0
9 weeks, 6 and 12 months post enrolment
Secondary outcome [5] 371918 0
Fundamental motor skills (FMS) Proficiency. Test of Gross Motor Development 3rd Edition (TGMD-3) will be used to measure movement competency relative to 13 FMS’s subdivided into two subscales: locomotor and object control (ball) skills as per SOPs.
Timepoint [5] 371918 0
9 weeks, 6 and 12 months post enrolment
Secondary outcome [6] 371919 0
Moderate to vigorous physical activity (MVPA) proficiency: Measured using the ActiGraph GT3X+ accelerometer.Monitors will be attached to adjustable elastic belts and worn on the right hip for 7 days. Accelerometer data will be uploaded to a customized Excel macro for determination of time spent in sedentary, light, moderate, and vigorous intensity PA. Recorded activity counts will be classified into the aforementioned intensity categories using the cut-points developed by Evenson.
Timepoint [6] 371919 0
9 weeks, 6 and 12 months post enrolment
Secondary outcome [7] 372305 0
Safety of the intervention. Staff and parents will document the number, type and severity of adverse events that occur during and following the intervention. These will focus on exercise induced wheeze and injury.
Timepoint [7] 372305 0
Weeks 1 to 9 while the intervention is taking place.

Eligibility
Key inclusion criteria
1. Aged 6 – 12 years
2. Bronchiectasis confirmed on high resolution computed tomography (HRCT), or if more than 5 years since HRCT, under the regular care of a respiratory paediatrician
3. Greater than or equal to 1 acute pulmonary exacerbation in the past 12-months
4. Medically able to complete an exercise program as determined by treating physician
Minimum age
6 Years
Maximum age
12 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Medically unstable as determined by treating physician
2. Unstable emotional and/or behavioural problems
3. Recent musculoskeletal injury (e.g., muscle strain, sprains, fractures)
4. Underlying chronic illness other than BE (e.g., asthma, Cystic Fibrosis (CF), neurological or cardiac disorders)
5. Knowingly unable to attend any exercise sessions or follow-up clinical visits over the 12 months (eg. planned movement from the area)
6. Active participation in a clinical trial of another investigational drug/device or interventional therapy.
7. Other medical/psychosocial condition that the investigators/treating physicians consider should be excluded from the trial to prevent potential harm/risk to the subject or may adversely affect study outcomes.

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)
Study staff will have no access to treatment allocation codes until time of randomisation and group allocation which will occur through a secure password protected database (eg RedCap) or opaque sealed envelopes depending on site. At the time of randomisation, staff will select "randomise" on the database and the treatment allocation code will be generated.
Group allocation will be maintained in secure files that are inaccessible to blinded study personnel. The independent statistician will keep the randomisation code on file and emergency code break envelopes will be kept securely at the Centre for Child Health Research (CCHR), South Brisbane for use in case of an emergency.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A biostatistician not directly involved in the analysis of study results will prepare the study randomisation code. A randomisation blocking scheme will be used to ensure that balance between the two treatment groups is maintained. Participants will be randomised to groups A or B (1:1 allocation), using computer generated random permuted block sizes (block sizes two to eight). Randomisation will be stratified by site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Wait-list controls. Children allocated to the control group will be offered the exercise programme once they complete 12-months of study follow-up
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Participant groups for analysis
All subjects randomised with complete data will be eligible for inclusion in the modified intention-to-treat analyses (ITT). Subjects randomised who complete all study visits and procedures and for whom complete data are available will be eligible for inclusion in the as-per-protocol analyses (APP) which may or may not be included as sensitivity analyses.

Demographic analyses
Demographic data of children will be summarised as proportions and/or means (SD) or medians (IQR) of the selected characteristics by randomised group.

Primary endpoint analyses
For the primary aim, a binary regression model with a suitably chosen link function (e.g., logistic) will be used where the target variable is whether or not an exacerbation occurred over the 12-month study period for each subject. The main covariate of interest is the treatment group (exercise vs. wait-list control). Other covariates potentially influencing the target variable such as age and sex will be considered. Therefore the statistically determined treatment effect will be appropriately adjusted for unbalanced data with respect to the other important covariates retained in the regression model.

Secondary endpoint analyses
Between-group differences will be calculated for secondary outcomes - aerobic fitness (Peak VO2), habitual PA (objectively measured MVPA), HR-QoL (PedsQL), and lung function (FEV1). These will be tested immediately post intervention, at 6-months follow-up, and 12-months follow-up using linear regression with treatment group (exercise vs. wait-list control) as the main effect and baseline measures of the respective outcome, along with other potential confounders (e.g., age, sex), as covariates.

Safety of the intervention: descriptive analyses will be performed on the number, type and severity adverse events that occur during and following the intervention and presented by treatment group. Comparisons between groups will be performed using Student’s T-Test for continuous variables and chi2 tests for proportions

Economic evaluation: A within-trial cost-effectiveness analysis and cost-utility analysis will be conducted by AI Lung to determine whether therapeutic exercise represents ‘value for money’ compared to usual care over a 12-month period from a healthcare provider perspective. Intervention costs will be determined from the project financial records, including costs associated with therapist training and staff time to deliver programs. Pulmonary exacerbation costs (antibiotic treatment and time of clinical staff) will be taken from the Pharmaceutical Benefits Scheme and the appropriate clinical award wage rate. The outcome of interest will be the proportion of children with no exacerbations over 12-months for the cost-effectiveness analysis, and HR-QoL (measured using PedsQL) for the cost-utility analysis.

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 in Australia
Recruitment state(s)
NT,QLD
Recruitment hospital [1] 14078 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 14079 0
Gold Coast University Hospital - Southport
Recruitment hospital [3] 14080 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 26868 0
4101 - South Brisbane
Recruitment postcode(s) [2] 26869 0
4215 - Southport
Recruitment postcode(s) [3] 26870 0
0810 - Tiwi

Funding & Sponsors
Funding source category [1] 303114 0
Government body
Name [1] 303114 0
National Health & Medical Research Council
Address [1] 303114 0
16 Marcus Clarke St,
Canberra ACT 2601
Country [1] 303114 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
Musk Ave
Kelvin Grove QLD 4350
Country
Australia
Secondary sponsor category [1] 303110 0
None
Name [1] 303110 0
None
Address [1] 303110 0
None
Country [1] 303110 0
Other collaborator category [1] 280812 0
University
Name [1] 280812 0
Griffith University
Address [1] 280812 0
Gold Coast campus,
Cnr Parklands Drive and Olsen Avenue,
Southport QLD 4215
Country [1] 280812 0
Australia
Other collaborator category [2] 280813 0
University
Name [2] 280813 0
Menzies School of Health Research
Address [2] 280813 0
PO Box 41096
Casuarina NT 0811
Country [2] 280813 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 303666 0
Queensland Children's Hospital and Health Service HREC
Ethics committee address [1] 303666 0
L7, Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 303666 0
Australia
Date submitted for ethics approval [1] 303666 0
22/07/2019
Approval date [1] 303666 0
Ethics approval number [1] 303666 0
Ethics committee name [2] 303667 0
Top Health Health Services & Menzies School of Health Research HREC
Ethics committee address [2] 303667 0
PO Box 41096
Casuarina NT 0811
Ethics committee country [2] 303667 0
Australia
Date submitted for ethics approval [2] 303667 0
06/09/2019
Approval date [2] 303667 0
Ethics approval number [2] 303667 0

Summary
Brief summary
Children with bronchiectasis regularly experience exacerbations of their condition resulting in frequent hospitalisations and decreased of quality of life (QoL). Therapeutic exercise may reduce the incidence of acute exacerbations, which is a key predictor of future lung function decline and morbidity. This study aims to determine if a tailored, 8-week therapeutic exercise program delivered to children aged 6 to 12 years with bronchiectasis prevents acute respiratory exacerbations. The primary hypothesis is that children who undergo the exercise program will have fewer exacerbations over a 12-month period than children who do not receive the intervention.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 94430 0
Prof Stewart Trost
Address 94430 0
Queensland University of Technology
L6, Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Country 94430 0
Australia
Phone 94430 0
+61 7 3069 7301
Fax 94430 0
Email 94430 0
s.trost@qut.edu.au
Contact person for public queries
Name 94431 0
Prof Stewart Trost
Address 94431 0
Queensland University of Technology
L6, Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Country 94431 0
Australia
Phone 94431 0
+61 7 3069 7301
Fax 94431 0
Email 94431 0
s.trost@qut.edu.au
Contact person for scientific queries
Name 94432 0
Prof Stewart Trost
Address 94432 0
Queensland University of Technology
L6, Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Country 94432 0
Australia
Phone 94432 0
+61 7 3069 7301
Fax 94432 0
Email 94432 0
s.trost@qut.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data dictionary and all de-identified participant data underlying published results only. Additional de-identified data may be shared following discussion with the principal investigator.
When will data be available (start and end dates)?
Data will be available once the trial has been completed, the data have been unblinded and the primary manuscript has been published. The start date of IPD availability will be approximately 01/02/2024. No end date has been determined
Available to whom?
Data will be made available to other researchers in the field who express an interest in the data
Available for what types of analyses?
De-identified quantitative analyses.
How or where can data be obtained?
Requests for data must be made in writing to the Principal Investigator and accompanied by a relevant proposal for use of the data and any relevant ethics committee approvals.
What supporting documents are/will be available?
No other documents available
Summary results
No Results