Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000743662
Ethics application status
Approved
Date submitted
15/06/2014
Date registered
14/07/2014
Date last updated
14/07/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A cohort study to examine the effect of 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix, Registered Trademark) on the frequency of non-typeable Haemophilus influenzae (NTHi) infection in the upper and lower airways of children
Scientific title
Does prior immunization with PHiD-CV influence the frequency of NTHi detection in the upper and lower airways in children undergoing bronchoscopy?
Secondary ID [1] 284049 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Children at risk of chronic lung disease and undergoing bronchoscopy 291105 0
non-typeable Haemophilus influenzae (NTHi) infection 292217 0
Condition category
Condition code
Respiratory 291448 291448 0 0
Other respiratory disorders / diseases
Infection 292764 292764 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
PHiD-CV given as per the Northern Territory infant immunization schedule. Child is not observed for any set period of time. Observation consist of the bronchoscopy alveolar lavage results at the time-point when the procedure is undertaken for clinical purposes and not for research purposes. Thus there is no time limit of the observation period as the bronchoscopy is undertaken when the paediatrician (not related to the study) deemed the procedure is necessary
Intervention code [1] 288742 0
Not applicable
Comparator / control treatment
No PHiD-CV
Control group
Active

Outcomes
Primary outcome [1] 291434 0
Number of children with NTHi detected in the bronchoalveolar lavage at >=10E4 cfu/ml
Timepoint [1] 291434 0
At time of bronchoscopy. For subjects: at least one month post PHiD-CV immunisation.
Secondary outcome [1] 306761 0
Number of children with NTHi detected in the nasopharyngeal swab
Timepoint [1] 306761 0
At time of bronchoscopy
Secondary outcome [2] 306762 0
In subgroup where blood could be collected, secondary outcomes are cytokine levels from PBMC stimulation using PHA (Phytohemagglutanin) for adaptive responses (72 hours post stimulation)
Timepoint [2] 306762 0
Bloods collected at time of bronchoscopy (uncontrolled)
Secondary outcome [3] 308897 0
In subgroup where blood could be collected, secondary outcomes are cytokine levels from PBMC stimulation using LPS and Poly I:C for innate responses (24 hour post stimulation)
Timepoint [3] 308897 0
At time of blood collection opportunistically i.e like the bronchoscopy, the procedure is undertaken for clinical purposes and not for research purposes. Thus there is no time limit of the observation period as the bloods undertaken when the paediatrician (not related to the study) deemed the procedure is necessary

Eligibility
Key inclusion criteria
Subjects: Children undergoing bronchoscopy who have had at least one PHiD-CV dose more than a month before bronchoscopy

Comparator: Children undergoing bronchoscopy who have not had any PHiD-CV dose (Brisbane and/or Darwin)
Minimum age
1 Years
Maximum age
19 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously enrolled
Cystic fibrosis
Immunodeficiency
Interstitial lung disease

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
Vaccine effectiveness will be calculated from the number children who have had PHiD-CV with clinically important levels of NTHi will be compared to those who have not had PHiD-CV with clinically important levels of NTHi.

Comparisons between groups will consist of subjects vs. total controls (Brisbane and NT children).

Subanalysis will be performed comparing subjects with
(a) NT controls only, and
(b) Brisbane contemporaneous controls

Total number of children in study is expected to be >300 which comprises of at least 79 children who have received at least one dose of PHiD-CV. Our main comparison will be between the cohort of NT children with and without PHiD-CV immunization. We currently have BAL data (2007-2010) from 80 children (who have not had PHiD-CV) in the NT and 50% of these children have NTHi in their BAL. We expect to collect BAL from a further children from NT who have had various number of PHiD-CV doses.

Assuming a 45% reduction in the proportion of children who have NTHi in their BAL post PHiD-CV, the study provides 88% power (5% level of significance), if we have a minimum of 221 children. However, we will continue to enroll children until the end of 2014 and expect an approximated sample size of 250 (children vaccinated with PHiD-CV and controls).

In the subgroup with blood available, cytokine profile from PBMC stimulation will be compared between groups using unpaired T-tests or Mann–Whitney U test

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/04/2011
Actual
19/04/2011
Date of last participant enrolment
Anticipated
31/12/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
316
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT,QLD
Recruitment hospital [1] 2058 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [2] 2059 0
Royal Children's Hospital - Herston

Funding & Sponsors
Funding source category [1] 288679 0
Government body
Name [1] 288679 0
National Health and Medical Research Council
Country [1] 288679 0
Australia
Funding source category [2] 288680 0
Commercial sector/Industry
Name [2] 288680 0
GlaxoSmithKline
Country [2] 288680 0
United Kingdom
Funding source category [3] 288683 0
Charities/Societies/Foundations
Name [3] 288683 0
Financial Markets Foundation for children (Grant 2011-019)
Country [3] 288683 0
Australia
Primary sponsor type
University
Name
Menzies School of Health Research, Charles Darwin University
Address
PO Box 41096, Casuarina NT 0811, Australia
Country
Australia
Secondary sponsor category [1] 287388 0
Individual
Name [1] 287388 0
Prof Anne Chang
Address [1] 287388 0
Menzies School of Health Research
PO Box 41096, Casuarina NT 0811, Australia
Country [1] 287388 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290529 0
NT Department of Health & Community Services and Menzies School of Health Research
Ethics committee address [1] 290529 0
PO Box 41096, Casuarina NT 0811, Australia
Ethics committee country [1] 290529 0
Australia
Date submitted for ethics approval [1] 290529 0
Approval date [1] 290529 0
03/10/2007
Ethics approval number [1] 290529 0
07/63
Ethics committee name [2] 290530 0
Royal Children's Hospital, Brisbane
Ethics committee address [2] 290530 0
Herston Road, Herston, Queensland 4029
Ethics committee country [2] 290530 0
Australia
Date submitted for ethics approval [2] 290530 0
Approval date [2] 290530 0
18/03/2008
Ethics approval number [2] 290530 0
2003/017

Summary
Brief summary
The aims of our study are to:
1. Determine the frequency of NTHi infection (defined by >10E4 cfu/ml BAL) in the lower airways of children who have received PHiD-CV;
2. Determine the frequency of NTHi carriage in the upper airways of children who have received PHiD-CV; and
3. Evaluate the influence of PHiD-CV on the systemic adaptive immunity to NTHi in`children with chronic suppurative lung disease.
Trial website
Trial related presentations / publications
Public notes
Aim 3 will only be conducted in a subset of children. Data includes analysis of previously collected data (microbiology of the lower and upper airways)

Contacts
Principal investigator
Name 46098 0
Prof Anne B Chang
Address 46098 0
Qld Children's Respiratory Centre
Children's Health Services (Royal Children's Hospital)
Herston Rd
Herston
QLD 4029
Country 46098 0
Australia
Phone 46098 0
+61 7 3636 5270
Fax 46098 0
Email 46098 0
[email protected]
Contact person for public queries
Name 46099 0
Gabrielle McCallum
Address 46099 0
Menzies School of Health Research
Rocklands Road
Tiwi
NT
Country 46099 0
Australia
Phone 46099 0
+61 8 89228588
Fax 46099 0
Email 46099 0
[email protected]
Contact person for scientific queries
Name 46100 0
Anne Chang
Address 46100 0
Qld Children's Respiratory Centre
Children's Health Services (Royal Children's Hospital)
Herston Rd
Herston
QLD 4029
Country 46100 0
Australia
Phone 46100 0
+61 7 3636 5270
Fax 46100 0
Email 46100 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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