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Trial registered on ANZCTR


Registration number
ACTRN12612000010897
Ethics application status
Approved
Date submitted
21/12/2011
Date registered
4/01/2012
Date last updated
5/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Antibiotics for treatment of bronchiectasis exacerbations in children - The Bronchiectasis Exacerbation Study (Study 2).
Scientific title
A randomised, double blind trial of Azithromycin versus Amoxycillin-Clavulate to treat mild to moderate respiratory exacerbations in children with non-Cystic Fibrosis bronchiectasis, Study Two.
Secondary ID [1] 279635 0
Nil
Universal Trial Number (UTN)
U1111-1126-5676
Trial acronym
BEST - 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchiectasis 285435 0
Condition category
Condition code
Respiratory 285616 285616 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Daily oral Azithromycin 5mg/kg for 21 days
Arm 2: Twice daily oral Amoxycillin-Clavulanic Acid 22.5mg/kg for 21 days

These treatments are administered at the onset of respiratory exacerbation after enrolment, and are administered only for one respiratory exacerbation.
Intervention code [1] 283915 0
Treatment: Drugs
Comparator / control treatment
Arm 1 recieves ACTIVE azithromycin and PLACEBO amoxycillin-clavulanic acid

Arm 2 receives PLACEBO azithromycin and ACTIVE amoxycillin-clavulanic acid
Control group
Active

Outcomes
Primary outcome [1] 286178 0
The proportion of children with resolution of the respiratory exacerbation (defined by return to baseline state of signs and symptoms). Baseline stat is determined by physician assessment of cough, sputum color and chest sounds at time of enrolment into study protocol.
Timepoint [1] 286178 0
21 days after initiation of treatment (Azithromycin OR Amoxycillin-Clavulanic acid).
Secondary outcome [1] 295312 0
Detectable difference in PC-QOL (Parent Cough-specific Quality of Life) measurement (minimum important difference between groups =0.9). This is a validated quality of life measure specific to paediatric cough, completed by the parent.
Timepoint [1] 295312 0
Day 21
Secondary outcome [2] 295313 0
Duration of exacerbation symptoms (symptoms of exacerbation are considered increased or changed quality of cough, increased sputum production or change in patient's normal sputum colour or purulence). This outcome is assessed by parental reporting of exacerbation symptoms (cough) and physician clinical review.
Timepoint [2] 295313 0
Measured from onset of symptoms of respiratory exacerbation until resolution of symptoms (return to baseline state, see primary outcome above).
Secondary outcome [3] 295314 0
Requirement for hospitalisation for respiratory exacerbations.
Timepoint [3] 295314 0
Measured at time of hospitalisation (if applicable) or resolution of symptoms. This outcome is measured from onset of exacerbation symptoms until resolution of exacerbation symptoms. Overall monitoring of exacerbation symptoms and requirement for hospitalisation is measured from enrolment for up to 18 months.
Secondary outcome [4] 295322 0
Detectable difference in serum laboratory assays: CRP, serum amyloid a, IL-6, IL-10, IP-10 (this outcome is only assessed where possible, i.e. not in all participants).
Timepoint [4] 295322 0
Measured at baseline, and onset and resolution of respiratory exacerbations. Total duration of outcome assessment is from enrolment for up to 18 months.
Secondary outcome [5] 295323 0
Presence and prevalence of viral and bacterial respiratory pathogens and antibioic (penicillin and macrolide) resistance of pathogens, on nasal swabs and sputum samples.
Timepoint [5] 295323 0
Measured at baseline, onset and resolution of exacerbations (sputum); measured at baseline, onset, middle and end of exacerbations (nasal swabs). Total duration of outcome assessment is from enrolment for up to 18 months.

Eligibility
Key inclusion criteria
Aged less than 18 years.
Bronchiectasis, as defined by HRCT scan within the last 5-years OR followed by a respiratory physician for treatment of bronchiectasis if diagnosed earlier.
2 or more respiratory exacerbations of bronchiectasis symptoms in the last 18 months prior to study enrolment.
Minimum age
No limit
Maximum age
19 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cystic Fibrosis (sweat chloride >35mmol/L or gene mutation). Liver dysfunction. Severe (hypoxic, dyspnoea or hospitalisation required) or recent exacerbation (in the last 4 weeks prior to study enrollment. Known hypersensitivity to macrolides or penicillins. Taking regular maintenance antibiotics of the same class as the investigational antibiotics (macrolides and penicillins), or has taken macrolides or penicillins within 3 weeks of study enrolment. Current or recent (within 4 months prior to study enrolment) identification of pseudomonas organism in the airways. Current treatment for an oncology condition of any kind.

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)
Sequential allocation list with each next position concealed by opaque covering.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block design, stratified by study site, age and aetiology of condition.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/03/2012
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
18/11/2016
Date of last data collection
Anticipated
Actual
18/05/2017
Sample size
Target
170
Accrual to date
Final
178
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD
Recruitment postcode(s) [1] 4786 0
4000
Recruitment postcode(s) [2] 4788 0
2000
Recruitment outside Australia
Country [1] 4029 0
New Zealand
State/province [1] 4029 0
Auckland

Funding & Sponsors
Funding source category [1] 284416 0
Government body
Name [1] 284416 0
National Health and Medical Research Council
Country [1] 284416 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Qld Children's Medical Research Institute
Address
Queensland Children's Health Service
(Lady Cilento Children's Hospital), Stanley Street, South Brisbane, Qld 4101
Country
Australia
Secondary sponsor category [1] 283343 0
Other Collaborative groups
Name [1] 283343 0
Menzies School of Health Research
Address [1] 283343 0
Building 58,
Royal Darwin Hospital
Tiwi, NT, 0811
Country [1] 283343 0
Australia
Other collaborator category [1] 260410 0
Hospital
Name [1] 260410 0
The Children's Hospital at Westmead
Address [1] 260410 0
Cnr Hawkesbury and Hainsworth St
Westmead, NSW 2145
Country [1] 260410 0
Australia
Other collaborator category [2] 260411 0
Hospital
Name [2] 260411 0
The Princess Margaret Hospital for Children
Address [2] 260411 0
Roberts Rd
Subiaco
WA 6008
Country [2] 260411 0
Australia
Other collaborator category [3] 260772 0
Hospital
Name [3] 260772 0
Starship Children's Hospital
Address [3] 260772 0
Park Road, Auckland, Private Bag 92024, Auckland 1142
Country [3] 260772 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286372 0
Children's Health Services Human Research Ethics Committee (EC00175)
Ethics committee address [1] 286372 0
Children's Health Services (Lady CIlento Children's Hospital), Stanley Street, South Brisbane, QLD 4101
Ethics committee country [1] 286372 0
Australia
Date submitted for ethics approval [1] 286372 0
16/01/2012
Approval date [1] 286372 0
02/02/2012
Ethics approval number [1] 286372 0
HREC/12/QRCH/5
Ethics committee name [2] 286373 0
Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research (EC00153)
Ethics committee address [2] 286373 0
John Matthew Building (Building 58)
Royal Darwin Hospital Campus
PO Box 41096
Casuarina NT 0811
Ethics committee country [2] 286373 0
Australia
Date submitted for ethics approval [2] 286373 0
18/01/2012
Approval date [2] 286373 0
13/03/2012
Ethics approval number [2] 286373 0
HREC-2012-175
Ethics committee name [3] 286374 0
Princess Margaret Hospital for Children Ethics Committee (EC00268)
Ethics committee address [3] 286374 0
Ethics Committee, Level 1
Princess Margaret Hospital for Children
GPO Box D184
Perth WA 6840
Ethics committee country [3] 286374 0
Australia
Date submitted for ethics approval [3] 286374 0
16/01/2012
Approval date [3] 286374 0
Ethics approval number [3] 286374 0
1968/EP
Ethics committee name [4] 286375 0
Sydney Children's Hospitals Network Human Research Ethics Committee (EC00130)
Ethics committee address [4] 286375 0
The Research Ethics Manager
The Research Office
Children's Hospital at Westmead
Locked Bag 4001
Westmead, NSW, 2145
Ethics committee country [4] 286375 0
Australia
Date submitted for ethics approval [4] 286375 0
16/01/2012
Approval date [4] 286375 0
Ethics approval number [4] 286375 0
12/SCHN/27
Ethics committee name [5] 286376 0
The University of Queensland Medical Research Ethics Committee (EC00179)
Ethics committee address [5] 286376 0
Ethics Officer
Research and Innovation Division
Cumbrae-Stewart Building (72)
The University of Qld (St Lucia) QLD, 4072
Ethics committee country [5] 286376 0
Australia
Date submitted for ethics approval [5] 286376 0
15/02/2012
Approval date [5] 286376 0
23/02/2012
Ethics approval number [5] 286376 0
2012000188
Ethics committee name [6] 287167 0
Northern X Health and Disability Ethics Committee
Ethics committee address [6] 287167 0
Ministry for Health, Private Bag 92-552, Wellesley St, Auckland
Ethics committee country [6] 287167 0
New Zealand
Date submitted for ethics approval [6] 287167 0
Approval date [6] 287167 0
Ethics approval number [6] 287167 0

Summary
Brief summary
Our national study aims to improve the management of bronchiectasis in children, a lung condition that is common in Indigenous people worldwide, and also occurs in non-Indigenous people. This study aims to discover whether treating respiratory exacerbations with one of two different oral antibiotics is more effective at resolving the exacerbation. The results of this study will impact on national and international guidelines and substantially advance knowledge on exacerbations of childhood bronchiectasis.
Trial website
Nil
Trial related presentations / publications
A. B. Chang, K. Grimwood, A. C. Wilson, P. P. van Asperen, C. A. Byrnes, K. A. Fo Grady, T. P. Sloots, C. F. Robertson, P. J. Torzillo, G. B. McCallum, I. B. Masters, H. M. Buntain, I. M. Mackay, J. Ungerer, J. Tuppin, and P. S. Morris. Bronchiectasis Exacerbation Study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial. Trials 14 (1):53, 2013.
Public notes

Contacts
Principal investigator
Name 33557 0
Prof Anne Chang
Address 33557 0
Menzies School of Health Research Rockland's Road, Tiwi, Darwin, NT 0810, Australia and Lady Cilento Children's Hospital, South Brisbane, Qld 4101
Country 33557 0
Australia
Phone 33557 0
+61 7 30681111
Fax 33557 0
Email 33557 0
anne_b_chang@health.qld.gov.au
Contact person for public queries
Name 16804 0
Prof Professor Anne Chang
Address 16804 0
Dept of Respiratory Medicine
Level 5, Lady Cilento Children's Hospital
Children's Health Services
Stanley St
Country 16804 0
Australia
Phone 16804 0
+61 7 30681111
Fax 16804 0
Email 16804 0
anne_b_chang@health.qld.gov.au
Contact person for scientific queries
Name 7732 0
Prof Professor Anne Chang
Address 7732 0
Children's Health Services (Lady Cilento Children's Hospital)
Stanley St
South Brisbane
QLD 4101
Country 7732 0
Australia
Phone 7732 0
+61 7 30681111
Fax 7732 0
Email 7732 0
anne_b_chang@health.qld.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary