Brief Title
Prevention of Bronchiectasis in Infants With Cystic Fibrosis
Official 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.
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: Nicholas deKlerk 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 endpoint is the proportion of children with radiologically-defined bronchiectasis 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
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Proportion of children with radiologically-defined bronchiectasis
Secondary Outcome
extent and severity of bronchiectasis
Condition
Cystic Fibrosis
Intervention
Azithromycin
Study Arms / Comparison Groups
azithromycin liquid preparation
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
132
Start Date
April 2012
Completion Date
May 2021
Primary Completion Date
May 2020
Eligibility Criteria
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 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
Gender
All
Ages
6 Weeks - 6 Months
Accepts Healthy Volunteers
No
Contacts
Peter D Sly, MMBS MD DSc, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT01270074
Organization ID
AZI001
Secondary IDs
STICK10K0
Responsible Party
Principal Investigator
Study Sponsor
The University of Queensland
Collaborators
Telethon Kids Institute
Study Sponsor
Peter D Sly, MMBS MD DSc, Study Chair, The University of Queensland
Verification Date
November 2019