Title
Prevention of Bronchiectasis in Infants With Cystic Fibrosis
A Phase 3 Multi-centre Randomised Placebo-controlled Study of Azithromycin in the Primary Prevention of Radiologically-defined Bronchiectasis in Infants With Cystic Fibrosis.
Phase
Phase 3Lead Sponsor
University of QueenslandStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Cystic Fibrosis BronchiectasisIntervention/Treatment
azithromycin ...Study Participants
130The 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.
SYNOPSIS OF PROTOCOL
Title Multi-centre randomized placebo-controlled study of azithromycin in the primary prevention of radiologically-defined bronchiectasis in infants with Cystic Fibrosis
Clinical Phase Phase 3
Protocol Number: AZI001
TGA Reference Number:
Protocol Co-Chairs: Peter D. Sly & Stephen M. Stick Microbiology Consultant: Lisa Saiman CT Consultant: Harm Tiddens Statistical Consultant: Robert S Ware
Study Design Randomized, double-blind parallel groups. Participants will be randomized into one of the following 2 groups on a 1:1 ratio with 65 participants per group;
Group A: 10 mg/kg (as 200mg/5ml) azithromycin three times weekly for three years added to standard CF therapy.
Group B: matched placebo three times weekly for three years added to standard CF therapy.
Accrual Objective 130 children
Accrual Period 24 months
Study Duration 36 months
Countries: Australia and New Zealand
Sites: Brisbane Au, Sydney, Au, Melbourne Au, Adelaide Au, Perth Au,Auckland Nz, Christchurch Nz.
Primary Endpoint The primary endpoints are the proportion of children with radiologically-defined bronchiectasis at age 3 years, and the proportion of lung tissue affected by disease at age 3 years.
Secondary Endpoints
The extent and severity of bronchiectasis at age 3 years
The volume of trapped gas at age 3 years
CF-related quality of life
Time to first pulmonary exacerbation
Proportion of participants experiencing a pulmonary exacerbation
Number of courses of inhaled or oral antibiotics
Number of days of inhaled antibiotics
Incidence of hospitalizations/Accident and Emergency department (A&E) visits for an acute respiratory exacerbation
Number of days hospitalized for an acute respiratory exacerbation
Number of days if intravenous antibiotics
Body mass index at 3 years of age.
Exploratory Endpoints
Markers of neutrophilic inflammation
Markers of oxidative stress
Composition of airway flora
Safety Endpoints
Proportion of participants growing P. aeruginosa in BAL
Age of acquisition of P. aeruginosa in BAL
Emergence of macrolide-resistant S. aureus, small colony variant S. aureus and non-tuberculous mycobacteria (NTM)
Treatment-related adverse events
Haematology and clinical chemistry
Inclusion Criteria Participants who meet all of the following criteria are eligible for enrolment as study participants:
Children of either sex with a diagnosis of CF following detection via New Born Screening (NBS) for cystic fibrosis
Participants who, in the opinion of the Investigator, are able to comply with the protocol for its duration
Written informed consent signed and dated by parent/legal guardian according to local regulations
Exclusion Criteria Participants who meet any of these criteria are not eligible for enrolment as trial participants:
Born <30 weeks gestation
Prolonged mechanical ventilation in the first 3 months of life
Participation in another randomized controlled trial within the 3 months preceding inclusion in this study
A significant medical disease or condition other than CF that is likely to interfere with the child's ability to complete the entire protocol
Previous major surgery except for meconium ileus
Macrolide hypersensitivity
Treatment Description ZITHROMAX® (azithromycin)
Study Procedures The study participants will be stratified by investigational site and randomly assigned to either azithromycin or placebo for three years.
Statistical Considerations Participants will be randomized in blocks to the treatment group or the placebo group using a one-to-one ratio. Randomization will be stratified by study site. This will ensure an approximately equal allocation to each group within each site.
Interim Analyses Interim analyses will occur when the first 50% of children (n=33 per group have completed the 12 month CT and when all subjects have completed the 12 month CT. Interim analyses will determine safety or success (unethical to continue).
Stopping Rules Study enrolment may be stopped if any of the following events occur:
Death of a participant that is related to study treatment.
The trial meets the definition of futility or success at either of the planned interim analyses
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
inert liquid preparation will be given three times per week from three months of age to three years of age
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
inert liquid preparation will be given three times per week from three months of age to three years of age
Inclusion Criteria: Children of either sex with a diagnosis of CF following detection via New Born Screening (NBS) for cystic fibrosis Participants who, in the opinion of the Investigator, are able to comply with the protocol for its duration Written informed consent signed and dated by parent/legal guardian according to local regulations Exclusion Criteria: Born <30 weeks gestation Prolonged mechanical ventilation in the first 3 months of life Participation in another randomized controlled trial within the 3 months preceding inclusion in this study A significant medical disease or condition other than CF that is likely to interfere with the child's ability to complete the entire protocol Previous major surgery except for meconium ileus Macrolide hypersensitivity
