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Prevention of Bronchiectasis in Infants With Cystic Fibrosis (COMBATCF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01270074
Recruitment Status : Active, not recruiting
First Posted : January 5, 2011
Last Update Posted : December 2, 2019
Sponsor:
Collaborator:
Telethon Kids Institute
Information provided by (Responsible Party):
Peter Sly, The University of Queensland

Tracking Information
First Submitted Date  ICMJE December 23, 2010
First Posted Date  ICMJE January 5, 2011
Last Update Posted Date December 2, 2019
Study Start Date  ICMJE April 2012
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2011)
Proportion of children with radiologically-defined bronchiectasis [ Time Frame: at three years of age ]
bronchiectasis will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
  • extent and severity of bronchiectasis [ Time Frame: at three years of age ]
    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 ]
    Quality of life questionnaire to be measured at 3 years
  • time to first pulmonary exacerbation [ Time Frame: over the first three years of life ]
    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 ]
    pulmonary exacerbation will be defined using a standardized instrument
  • body mass index [ Time Frame: 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 growing Pseudomonas aeruginosa in bronchoalveolar lavage [ Time Frame: 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 [ Time Frame: over the first three years of life ]
  • Emergence of macrolide-resistant Staphylococcus aureus, small colony variant Staphylococcal aureus and non-tuberculous mycobacterium [ Time Frame: over the first three years of life ]
  • Volume of trapped gas at age 3 years [ Time Frame: at 3 years ]
    air trapping will be determined from a low dose volumetric chest computed tomography scan performed at 3 years of age
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2011)
  • extent and severity of bronchiectasis [ Time Frame: at three years of age ]
  • CF-related quality of life [ Time Frame: at three years of age ]
  • time to first pulmonary exacerbation [ Time Frame: over the first three years of life ]
    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 ]
  • body mass index [ Time Frame: 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 growing Pseudomonas aeruginosa in bronchoalveolar lavage [ Time Frame: 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 [ Time Frame: over the first three years of life ]
  • Emergence of macrolide-resistant Staphylococcus aureus, macrolide-resistant Haemophilus influenzae, small colony variant Staphylococcal aureus and non-tuberculous mycobacterium [ Time Frame: over the first three years of life ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Bronchiectasis in Infants With Cystic Fibrosis
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Cystic Fibrosis
  • Bronchiectasis
Intervention  ICMJE
  • 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
  • Drug: Placebo control
    inert liquid preparation will be given three times per week from three months of age to three years of age
Study Arms  ICMJE
  • 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
    Intervention: Drug: Azithromycin
  • 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
    Intervention: Drug: Placebo control
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 27, 2019)
132
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2011)
130
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Weeks to 6 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01270074
Other Study ID Numbers  ICMJE AZI001
STICK10K0 ( Other Grant/Funding Number: Cystif Fibrosis Foundation Therapeutics, INc. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Clinical Study Report (CSR)
Responsible Party Peter Sly, The University of Queensland
Study Sponsor  ICMJE The University of Queensland
Collaborators  ICMJE Telethon Kids Institute
Investigators  ICMJE
Study Chair: Peter D Sly, MMBS MD DSc The University of Queensland
Study Chair: Stephen M Stick, MBBChir PhD Telethon Kids Institute
PRS Account The University of Queensland
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP