Prevention of Bronchiectasis in Infants With Cystic Fibrosis
- Conditions
- BronchiectasisCystic Fibrosis
- Interventions
- Drug: Placebo control
- Registration Number
- NCT01270074
- Lead Sponsor
- The University of Queensland
- 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.
- Detailed Description
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:
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
Exclusion Criteria Participants who meet any of these criteria are not eligible for enrolment as trial participants:
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
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description azithromycin liquid preparation Azithromycin 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 Placebo control inert liquid preparation will be given three times per week from three months of age to three years of age
- Primary Outcome Measures
Name Time Method Proportion of children with radiologically-defined bronchiectasis at three years of age bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
The proportion of lung tissue affected by disease at three years of age Percentage of diseased lung will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
- Secondary Outcome Measures
Name Time Method body mass index at three years of age body mass index will be calcualted from hieight and weight measurements taken at 3 years of age.
proportion of participants experiencing a pulmonary exacerbation over the first three years of life pulmonary exacerbation will be defined using a standardized instrument
time to first pulmonary exacerbation over the first three years of life pulmonary exacerbation will be defined using a standardized instrument
Volume of trapped gas at age 3 years at 3 years air trapping will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
extent and severity of bronchiectasis at three years of age bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
Proportion of participants growing Pseudomonas aeruginosa in bronchoalveolar lavage over the first three years of life bronchoalveolar lavage will be performed at 3 months, 1 year and 3 years of age
age of acquisition of Pseudomonas aeruginosa over the first three years of life CF-related quality of life at three years of age Quality of life questionnaire to be measured at 3 years
Emergence of macrolide-resistant Staphylococcus aureus, small colony variant Staphylococcal aureus and non-tuberculous mycobacterium over the first three years of life
Trial Locations
- Locations (9)
Sydney Children's Hospital
🇦🇺Sydney, New South Wales, Australia
Perth Children's Hospital
🇦🇺Perth, Western Australia, Australia
Queensland Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Monash Medical Centre
🇦🇺Melbourne, Victoria, Australia
Starship Hospital
🇳🇿Auckland, New Zealand
Westmead Children's Hospital
🇦🇺Sydney, New South Wales, Australia
Mater Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Women's and Children's Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Children's Hospital
🇦🇺Melbourne, Victoria, Australia