Prevention of Bronchiectasis in Infants With Cystic Fibrosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis Bronchiectasis	Drug: Azithromycin Drug: Placebo control	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
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.

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Azithromycin Azithromycin dihydrate Azithromycin monohydrate

U.S. FDA Resources

Further study details as provided by Queensland Children's Medical Research Institute:

Primary Outcome Measures:

Proportion of children with radiologically-defined bronchiectasis [ Time Frame: at three years of age ] [ Designated as safety issue: No ]
bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age

Secondary Outcome Measures:

extent and severity of bronchiectasis [ Time Frame: at three years of age ] [ Designated as safety issue: No ]
bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
CF-related quality of life [ Time Frame: at three years of age ] [ Designated as safety issue: No ]
Quality of life questionnaire to be measured at 3 years
time to first pulmonary exacerbation [ Time Frame: over the first three years of life ] [ Designated as safety issue: No ]
pulmonary exacerbation will be defined using a standardized instrument
proportion of participants experiencing a pulmonary exacerbation [ Time Frame: over the first three years of life ] [ Designated as safety issue: No ]
pulmonary exacerbation will be defined using a standardized instrument
body mass index [ Time Frame: at three years of age ] [ Designated as safety issue: No ]
body mass index will be calcualted from hieight and weight measurements taken at 3 years of age.
Proportion of participants growing Pseudomonas aeruginosa in bronchoalveolar lavage [ Time Frame: over the first three years of life ] [ Designated as safety issue: Yes ]
bronchoalveolar lavage will be performed at 3 months, 1 year and 3 years of age
age of acquisition of Pseudomonas aeruginosa [ Time Frame: over the first three years of life ] [ Designated as safety issue: Yes ]
Emergence of macrolide-resistant Staphylococcus aureus, small colony variant Staphylococcal aureus and non-tuberculous mycobacterium [ Time Frame: over the first three years of life ] [ Designated as safety issue: Yes ]
Volume of trapped gas at age 3 years [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
air trapping will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age

Estimated Enrollment:	130
Study Start Date:	April 2012
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	Drug: 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 Other Name: Zithromax
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	Drug: Placebo control inert liquid preparation will be given three times per week from three months of age to three years of age

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Eligibility

Ages Eligible for Study:	6 Weeks to 6 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01270074

Locations

Australia, New South Wales
Sydney Children's Hospital
Sydney, New South Wales, Australia
Westmead Children's Hospital
Sydney, New South Wales, Australia
Australia, Queensland
Royal Children's Hospital
Brisbane, Queensland, Australia
Mater Children's Hospital
Brisbane, Queensland, Australia
Australia, South Australia
Women's and Children's Hospital
Adelaide, South Australia, Australia
Australia, Victoria
Royal Children's Hospital
Melbourne, Victoria, Australia
Monash Medical Centre
Melbourne, Victoria, Australia
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
New Zealand
Starship Hospital
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand

Sponsors and Collaborators

Queensland Children's Medical Research Institute

Telethon Institute for Child Heath Research

Investigators

Study Chair:	Peter D Sly, MMBS MD DSc	Queensland Children's Medical Research Institute
Study Chair:	Stephen M Stick, MBBChir PhD	Telethon Institute for Child Health Research

More Information

Additional Information:

The Australia Respiratory Early Surveillance Team for Cystic Fibrosis This link exits the ClinicalTrials.gov site

Queensland Children's Medical Research Institute This link exits the ClinicalTrials.gov site

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. 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. 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. Epub 2009 Jul 19.

Responsible Party:	Peter Sly, Protocol co-chair, Queensland Children's Medical Research Institute
ClinicalTrials.gov Identifier:	NCT01270074 History of Changes
Other Study ID Numbers:	AZI001, STICK10K0
Study First Received:	December 23, 2010
Last Updated:	May 16, 2012
Health Authority:	Australia: Human Research Ethics Committee New Zealand: Medsafe

Keywords provided by Queensland Children's Medical Research Institute:

double blind placebo controlled randomised clinical trial
azithromycin
infant

pediatric
cystic fibrosis
bronchiectasis

Additional relevant MeSH terms:

Bronchiectasis
Cystic Fibrosis
Fibrosis
Bronchial Diseases
Respiratory Tract Diseases
Pancreatic Diseases
Digestive System Diseases
Lung Diseases

Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013

Prevention of Bronchiectasis in Infants With Cystic Fibrosis (COMBATCF)