Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000011886
Ethics application status
Approved
Date submitted
21/12/2011
Date registered
4/01/2012
Date last updated
16/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Antibiotics for bronchiectasis exacerbations in children - The Bronchiectasis Exacerbation Study (Study 1).
Scientific title
A randomised, double blind, placebo controlled trial of Azithromycin versus Amoxycillin-Clavulanic Acid to treat mild to moderate respiratory exacerbations in children with non-Cystic Fibrosis bronchiectasis, Study One.
Secondary ID [1] 273613 0
Nil
Universal Trial Number (UTN)
U1111-1126-4148
Trial acronym
BEST - 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchiectasis 285410 0
Condition category
Condition code
Respiratory 285590 285590 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Daily oral Azithromycin 5mg/kg for 14 days
Arm 2: Twice daily oral Amoxycillin-Clavulanic Acid 22.5mg/kg for 14 days
Arm 3: oral placebo for 14 days

These treatments are administered at the onset of respiratory exacerbation symptoms after enrolment, and are continued for one exacerbation only.
Intervention code [1] 283899 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

Arm 3 recieves PLACEBO azithromycin and PLACEBO amoxycillin-clavulanic acid
Control group
Placebo

Outcomes
Primary outcome [1] 286156 0
The proportion of children with resolution of the respiratory exacerbation (defined by return to baseline state of signs and symptoms). Baseline state is determined by physician assessment at time of study enrolment, and consists of assessment of patient's cough, sputum color, and chest sounds.
Timepoint [1] 286156 0
14 days after initiation of treatment (Azithromycin OR Amoxycillin-Clavulanic acid OR Placebo).
Secondary outcome [1] 295284 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 pediatric cough, completed by the parent.
Timepoint [1] 295284 0
Day 14.
Secondary outcome [2] 295285 0
Time of onset to next respiratory exacerbation, assessed by monthly parent follow up calls and 3-monthly clinical assessment by respiratory physician.
Timepoint [2] 295285 0
Measured from resolution of respiratory exacerbation until onset of next exacerbation (measured for up to 6 months after resolution of prior exacerbation).
Secondary outcome [3] 295286 0
Duration of exacerbation symptoms, assessed by parental recording of cough and sputum production.
Timepoint [3] 295286 0
Measured from onset of symptoms of respiratory exacerbation until resolution of symptoms (return to baseline state, see primary outcome above for determination of baseline state).
Secondary outcome [4] 295287 0
Requirement for hospitalisation for respiratory exacerbations.
Timepoint [4] 295287 0
Measured at time of hospitalisation (if applicable) or resolution of symptoms. Measured from enrolment for up to 18 months.
Secondary outcome [5] 295290 0
Detectable difference in serum laboratory assays: CRP, serum amyloid a, IL-6, IL-10, IP-10 (Only done when possible i.e not all children will have bloods taken).
Timepoint [5] 295290 0
Measured at baseline, and start and end of respiratory exacerbations. Total duration 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 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 (defined as measurement of sweat chloride >35mmol/L or by gene mutation). Liver dysfunction. Severe (hypoxic, dyspnoea or hospitalisation required) or recent exacerbation (in the 4 weeks prior to study enrolment). Known hypersensitivity to penicillins or macrolides. Taking regular maintenance antibiotics of the same class as the investigational antibiotics (macrolides and penicillins), or has taken macrolides or penicillins in the 3 weeks prior to study enrolment. Current or recent (within 4 months prior to study enrolment) identification of pseudomonas organism in the airways.

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?



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
3/07/2012
Date of last participant enrolment
Anticipated
Actual
19/05/2017
Date of last data collection
Anticipated
Actual
19/12/2017
Sample size
Target
189
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
NT,QLD,WA
Recruitment postcode(s) [1] 4781 0
4000
Recruitment postcode(s) [2] 4783 0
2000
Recruitment postcode(s) [3] 4785 0
0800
Recruitment postcode(s) [4] 22672 0
6000 - Perth
Recruitment outside Australia
Country [1] 4022 0
New Zealand
State/province [1] 4022 0
Auckland

Funding & Sponsors
Funding source category [1] 284391 0
Government body
Name [1] 284391 0
National Health and Medical Research Council
Country [1] 284391 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] 283320 0
Other Collaborative groups
Name [1] 283320 0
Menzies School of Health Research
Address [1] 283320 0
Building 58,
Royal Darwin Hospital
Tiwi, NT 0811
Country [1] 283320 0
Australia
Other collaborator category [1] 260397 0
Hospital
Name [1] 260397 0
Address [1] 260397 0
Flemington Rd
Parkville
VIC 3052
Country [1] 260397 0
Australia
Other collaborator category [2] 260398 0
Hospital
Name [2] 260398 0
The Children's Hospital at Westmead
Address [2] 260398 0
Cnr Hawkesbury and Hainsworth St
Westmead, NSW 2145
Country [2] 260398 0
Australia
Other collaborator category [3] 260399 0
Hospital
Name [3] 260399 0
The Princess Margaret Hospital for Children
Address [3] 260399 0
Roberts Rd
Subiaco
WA 6008
Country [3] 260399 0
Australia
Other collaborator category [4] 260771 0
Hospital
Name [4] 260771 0
Starship Children's Hospital
Address [4] 260771 0
Park Road, Auckland
Private Bag 92024
Auckland 1142
Country [4] 260771 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286367 0
Children's Health Services Human Research Ethics Committee (EC00175)
Ethics committee address [1] 286367 0
Ethics committee country [1] 286367 0
Australia
Date submitted for ethics approval [1] 286367 0
17/01/2012
Approval date [1] 286367 0
02/02/2012
Ethics approval number [1] 286367 0
HREC/12/QRCH/5
Ethics committee name [2] 286368 0
Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research (EC00153)
Ethics committee address [2] 286368 0
Ethics committee country [2] 286368 0
Australia
Date submitted for ethics approval [2] 286368 0
18/01/2012
Approval date [2] 286368 0
13/03/2012
Ethics approval number [2] 286368 0
HREC-2012-1705
Ethics committee name [3] 286369 0
Princess Margaret Hospital for Children Ethics Committee (EC00268)
Ethics committee address [3] 286369 0
Ethics committee country [3] 286369 0
Australia
Date submitted for ethics approval [3] 286369 0
16/01/2012
Approval date [3] 286369 0
Ethics approval number [3] 286369 0
1968/EP
Ethics committee name [4] 286370 0
Sydney Children's Hospitals Network Human Research Ethics Committee (EC00130)
Ethics committee address [4] 286370 0
Ethics committee country [4] 286370 0
Australia
Date submitted for ethics approval [4] 286370 0
16/01/2012
Approval date [4] 286370 0
Ethics approval number [4] 286370 0
12/SCHN/27
Ethics committee name [5] 286371 0
The University of Queensland Medical Research Ethics Committee (EC00179)
Ethics committee address [5] 286371 0
Ethics committee country [5] 286371 0
Australia
Date submitted for ethics approval [5] 286371 0
15/02/2012
Approval date [5] 286371 0
23/02/2012
Ethics approval number [5] 286371 0
2012000188
Ethics committee name [6] 287166 0
Northern X Health and Disability Ethics Committee
Ethics committee address [6] 287166 0
Ethics committee country [6] 287166 0
New Zealand
Date submitted for ethics approval [6] 287166 0
Approval date [6] 287166 0
Ethics approval number [6] 287166 0

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

Contacts
Principal investigator
Name 33540 0
Prof Anne Chang
Address 33540 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 33540 0
Australia
Phone 33540 0
+61730682300
Fax 33540 0
Email 33540 0
[email protected]
Contact person for public queries
Name 16787 0
Professor Anne Chang
Address 16787 0
Children's Health Services (Lady CIlento Children's Hospital), Stanley Street, South Brisbane, QLD 4101
Country 16787 0
Australia
Phone 16787 0
+61730682300
Fax 16787 0
Email 16787 0
[email protected]
Contact person for scientific queries
Name 7715 0
Professor Anne Chang
Address 7715 0
Dept of Respiratory Medicine
Children's Health Services (Lady CIlento Children's Hospital), Stanley Street, South Brisbane, QLD 4101
Country 7715 0
Australia
Phone 7715 0
+61730682300
Fax 7715 0
Email 7715 0
[email protected]

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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Efficacy of oral amoxicillin–clavulanate or azithr... [More Details]
Study results articleYes

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAntibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial.2012https://dx.doi.org/10.1186/1745-6215-13-156
EmbaseEfficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial.2019https://dx.doi.org/10.1016/S2213-2600%2819%2930254-1
Dimensions AIEfficacy of oral amoxicillin–clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial2019https://doi.org/10.1016/s2213-2600(19)30254-1
N.B. These documents automatically identified may not have been verified by the study sponsor.