Prevention of Bronchiectasis in Infants With Cystic Fibrosis

NCT01270074 | Completed Phase 3 DMC

• 2 other identifiers: AZI001STICK10K0
• Study Type: interventional
• Target: 130
• Locations: 2 countries
• Sites: 10

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.

Conditions

Cystic Fibrosis; Bronchiectasis

Keywords

double blind placebo controlled randomised clinical trial; azithromycin; infant; pediatric; cystic fibrosis; bronchiectasis

Outcome Measures

Primary Outcomes (2)

• Proportion of children with radiologically-defined bronchiectasis

  bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age

  at three years of age

• The proportion of lung tissue affected by disease

  Percentage of diseased lung will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age

  at three years of age

Secondary Outcomes (9)

• extent and severity of bronchiectasis

  at three years of age

• CF-related quality of life

  at three years of age

• time to first pulmonary exacerbation

  over the first three years of life

• proportion of participants experiencing a pulmonary exacerbation

  over the first three years of life

• body mass index

  at three years of age

Study Arms (2)

azithromycin liquid preparation

EXPERIMENTAL

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

inert liquid preparation

ACTIVE COMPARATOR

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

Drug: Placebo control

Interventions

Azithromycin DRUG

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

Also known as: Zithromax

azithromycin liquid preparation

Placebo control DRUG

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

inert liquid preparation

Eligibility Criteria

• Age: 6 Weeks - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Born \<30 weeks gestation
• Prolonged mechanical ventilation in the first 3 months of life
• 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

Sponsors & Collaborators

• The University of Queensland: lead
• Telethon Kids Institute: collaborator

Study Sites (10)

Sydney Children's Hospital

Sydney, New South Wales, Australia

Location

Westmead Children's Hospital

Sydney, New South Wales, Australia

Location

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

Location

Mater Children's Hospital

Brisbane, Queensland, Australia

Location

Royal Children's Hospital

Brisbane, Queensland, Australia

Location

Women's and Children's Hospital

Adelaide, South Australia, Australia

Location

Monash Medical Centre

Melbourne, Victoria, Australia

Location

Royal Children's Hospital

Melbourne, Victoria, Australia

Location

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

Location

Starship Hospital

Auckland, New Zealand

Location

Related Publications (4)

• 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.

  PMID: 19010992 BACKGROUND

• 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.

  PMID: 19372250 BACKGROUND

• 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.

  PMID: 19616787 BACKGROUND

• 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.

  PMID: 35662406 DERIVED

Related Links

• The Australia Respiratory Early Surveillance Team for Cystic Fibrosis
• Telethon Institute for Child Health Research

MeSH Terms

Conditions

Cystic Fibrosis; Bronchiectasis

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Peter D Sly, MMBS MD DSc

  The University of Queensland

  STUDY CHAIR

• Stephen M Stick, MBBChir PhD

  Telethon Kids Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: January 5, 2011
• Study Start: April 1, 2012
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2021
• Last Updated: September 16, 2021

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR

Locations

NZ (1); AU (9)