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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01270074




Registration number
NCT01270074
Ethics application status
Date submitted
23/12/2010
Date registered
5/01/2011
Date last updated
16/09/2021

Titles & IDs
Public title
Prevention of Bronchiectasis in Infants With Cystic Fibrosis
Scientific title
A Phase 3 Multi-centre Randomised Placebo-controlled Study of Azithromycin in the Primary Prevention of Radiologically-defined Bronchiectasis in Infants With Cystic Fibrosis.
Secondary ID [1] 0 0
STICK10K0
Secondary ID [2] 0 0
AZI001
Universal Trial Number (UTN)
Trial acronym
COMBATCF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Bronchiectasis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azithromycin
Treatment: Drugs - Placebo control

Experimental: azithromycin liquid preparation - azithromycin will be given at a dose of 10mg/kg given three times per week from three months of age to three years of age

Active comparator: inert liquid preparation - inert liquid preparation will be given three times per week from three months of age to three years of age


Treatment: Drugs: Azithromycin
azithromycin will be given as a liquid preparation at a dose of 10 mg/kg three times per week from three months of age until three years of age

Treatment: Drugs: Placebo control
inert liquid preparation will be given three times per week from three months of age to three years of age
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of children with radiologically-defined bronchiectasis
Timepoint [1] 0 0
at three years of age
Primary outcome [2] 0 0
The proportion of lung tissue affected by disease
Timepoint [2] 0 0
at three years of age
Secondary outcome [1] 0 0
extent and severity of bronchiectasis
Timepoint [1] 0 0
at three years of age
Secondary outcome [2] 0 0
CF-related quality of life
Timepoint [2] 0 0
at three years of age
Secondary outcome [3] 0 0
time to first pulmonary exacerbation
Timepoint [3] 0 0
over the first three years of life
Secondary outcome [4] 0 0
proportion of participants experiencing a pulmonary exacerbation
Timepoint [4] 0 0
over the first three years of life
Secondary outcome [5] 0 0
body mass index
Timepoint [5] 0 0
at three years of age
Secondary outcome [6] 0 0
Proportion of participants growing Pseudomonas aeruginosa in bronchoalveolar lavage
Timepoint [6] 0 0
over the first three years of life
Secondary outcome [7] 0 0
age of acquisition of Pseudomonas aeruginosa
Timepoint [7] 0 0
over the first three years of life
Secondary outcome [8] 0 0
Emergence of macrolide-resistant Staphylococcus aureus, small colony variant Staphylococcal aureus and non-tuberculous mycobacterium
Timepoint [8] 0 0
over the first three years of life
Secondary outcome [9] 0 0
Volume of trapped gas at age 3 years
Timepoint [9] 0 0
at 3 years

Eligibility
Key inclusion criteria
1. Children of either sex with a diagnosis of CF following detection via New Born Screening (NBS) for cystic fibrosis
2. Participants who, in the opinion of the Investigator, are able to comply with the protocol for its duration
3. Written informed consent signed and dated by parent/legal guardian according to local regulations
Minimum age
6 Weeks
Maximum age
6 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Born <30 weeks gestation
2. Prolonged mechanical ventilation in the first 3 months of life
3. Participation in another randomized controlled trial within the 3 months preceding inclusion in this study
4. A significant medical disease or condition other than CF that is likely to interfere with the child's ability to complete the entire protocol
5. Previous major surgery except for meconium ileus
6. Macrolide hypersensitivity

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2021
Sample size
Target
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
Westmead Children's Hospital - Sydney
Recruitment hospital [3] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Mater Children's Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital - Adelaide
Recruitment hospital [7] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [8] 0 0
Royal Children's Hospital - Melbourne
Recruitment hospital [9] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Telethon Kids Institute
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The general aim of this project is to conduct a randomized, double-blind, placebo-controlled clinical trial of azithromycin to determine whether treatment from infancy is safe and will prevent the onset of bronchiectasis. One hundred and thirty infants will be recruited from CF clinics in Australia and New Zealand and treated from 3 months to three years of age. The primary outcome will be the proportion with radiologically-defined bronchiectasis at 3 years of age. Safety and mechanistic evaluations will also be undertaken.
Trial website
https://clinicaltrials.gov/study/NCT01270074
Trial related presentations / publications
Douglas TA, Brennan S, Gard S, Berry L, Gangell C, Stick SM, Clements BS, Sly PD. Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis. Eur Respir J. 2009 Feb;33(2):305-11. doi: 10.1183/09031936.00043108. Epub 2008 Nov 14.
Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF). Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med. 2009 Jul 15;180(2):146-52. doi: 10.1164/rccm.200901-0069OC. Epub 2009 Apr 16.
Stick SM, Brennan S, Murray C, Douglas T, von Ungern-Sternberg BS, Garratt LW, Gangell CL, De Klerk N, Linnane B, Ranganathan S, Robinson P, Robertson C, Sly PD; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J Pediatr. 2009 Nov;155(5):623-8.e1. doi: 10.1016/j.jpeds.2009.05.005. Epub 2009 Jul 19.
Stick SM, Foti A, Ware RS, Tiddens HAWM, Clements BS, Armstrong DS, Selvadurai H, Tai A, Cooper PJ, Byrnes CA, Belessis Y, Wainwright C, Jaffe A, Robinson P, Saiman L, Sly PD; COMBAT CF Study Group. The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial. Lancet Respir Med. 2022 Aug;10(8):776-784. doi: 10.1016/S2213-2600(22)00165-5. Epub 2022 Jun 2.
Public notes

Contacts
Principal investigator
Name 0 0
Peter D Sly, MMBS MD DSc
Address 0 0
The University of Queensland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01270074