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Trial registered on ANZCTR


Registration number
ACTRN12621001556831
Ethics application status
Approved
Date submitted
5/10/2021
Date registered
16/11/2021
Date last updated
18/10/2022
Date data sharing statement initially provided
16/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Efficacy of Bacterial Lysate in Prevention of Asthma
Scientific title
The Effect of Oral Bacterial Lysate to Prevent Persistent Wheeze in Infants After Severe Bronchiolitis; a Randomised Placebo-controlled Trial
Secondary ID [1] 305468 0
NCT05064631
Secondary ID [2] 305469 0
2021-000628-36
Universal Trial Number (UTN)
Trial acronym
BLIPA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Tract Infections 323851 0
Wheezing 323853 0
Condition category
Condition code
Respiratory 321360 321360 0 0
Other respiratory disorders / diseases
Infection 321361 321361 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bacterial Lysate. Bacterial lysate medicines are made from bacterial cells that are broken down and are intended to stimulate the immune system.

Experimental: Active intervention - Oral Broncho-Vaxom (3.5mg) administered daily for 10 (preferably consecutive) days per month for 24 months as oral powder mixed with food.

Adherence monitored through dosing diary and to return the completed diary to site on a monthly basis
Intervention code [1] 321875 0
Treatment: Drugs
Intervention code [2] 322045 0
Prevention
Comparator / control treatment
Placebo Comparator: Placebo control - Matched placebo administered daily for 10 days per month for 24 months. Placebo capsules will be of identical shape, colour, and size to the intervention. The placebo capsules consist of excipients.
Control group
Placebo

Outcomes
Primary outcome [1] 329142 0
Presence of a wheezing episode between 19 and 24 months - Parent or guardian reported wheeze between 19-24 months that is also confirmed by the presence of one or more of the following in the primary care record: salbutamol inhaler, active wheeze diagnosis, asthma diagnosis.
Timepoint [1] 329142 0
19-24 months after starting treatment
Secondary outcome [1] 401604 0
Prescription for more than one salbutamol inhaler between 19-24 months - Number of prescriptions for salbutamol inhalers as recorded on the primary care record between 19-24 months
Timepoint [1] 401604 0
19-24 months after starting treatment
Secondary outcome [2] 401605 0
Active wheeze diagnosis on primary care record between 19-24 months - Presence of an active wheeze diagnosis as recorded on the primary care record between 19-24 months
Timepoint [2] 401605 0
19-24 months after starting treatment
Secondary outcome [3] 401606 0
Asthma diagnosis on primary care record between 19-24 months - Presence of an asthma diagnosis as recorded on the primary care record between 19-24 months
Timepoint [3] 401606 0
19-24 months after starting treatment
Secondary outcome [4] 401607 0
Time to first episode of parent-reported wheeze during the 24 months since initiation of study drug - The time to first episode of parent-reported wheeze during the 24 months since initiation of study drug
Timepoint [4] 401607 0
0-24 months after starting treatment
Secondary outcome [5] 401608 0
Number of unscheduled medical attendances for wheeze between 19-24 months collected monthly from parents and checked with medical records
Timepoint [5] 401608 0
19-24 months after starting treatment
Secondary outcome [6] 401609 0
Number of hospital admissions for wheeze between 19-24 months from medical records
Timepoint [6] 401609 0
19-24 months after starting treatment
Secondary outcome [7] 401610 0
Number of days admitted to hospital for wheeze between 19-24 months, from medical records.
Timepoint [7] 401610 0
19-24 months after starting treatment
Secondary outcome [8] 401611 0
Number of unscheduled medical attendances for any lower respiratory symptoms between 19-24 months after starting treatment, collected from parents through e-records and/or phone calls
Timepoint [8] 401611 0
19-24 months after starting treatment
Secondary outcome [9] 401612 0
Number of courses of systemic corticosteroids for wheeze during the 24 months since initiation of study drug, using using diary reports and/or medical records
Timepoint [9] 401612 0
0-24 months after starting treatment
Secondary outcome [10] 401613 0
Number of courses of oral corticosteroids for wheeze between 19-24 months using using diary reports and/or medical records
Timepoint [10] 401613 0
19-24 months after starting treatment
Secondary outcome [11] 401614 0
Number of courses of antibiotics for wheeze between 19-24 months after starting treatment using using diary reports and/or medical records
Timepoint [11] 401614 0
19-24 months after starting treatment
Secondary outcome [12] 401615 0
Prescription for regular oral montelukast between 19-24 months after starting treatment using using diary reports and/or medical records
Timepoint [12] 401615 0
19-24 months after starting treatment
Secondary outcome [13] 401616 0
Parent reported eczema between 19-24 months after starting treatment
Timepoint [13] 401616 0
19-24 months after starting treatment
Secondary outcome [14] 401617 0
Eczema confirmed by U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. at 19-24 months. - Presence of Eczema confirmed by U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. between 19-24 months.
Timepoint [14] 401617 0
19-24 months after starting treatment
Secondary outcome [15] 401618 0
Incidence of adverse events for the treatment group between 0-24 months using using diary reports and/or medical records
Timepoint [15] 401618 0
0-24 months after starting treatment, using diary reports and/or medical records
Secondary outcome [16] 401619 0
Incidence of serious adverse events for the treatment group between 0-24 months, using diary reports and/or medical records collected monthly
Timepoint [16] 401619 0
0-24 months after starting treatment, using diary reports collected monthly
Secondary outcome [17] 401620 0
Incidence of SUSARs for the treatment group between 0-24 months after starting treatment, as reported in diary and/or medical records collected monthly
Timepoint [17] 401620 0
0-24 months after starting treatment, as reported in diary and/or medical records collected monthly
Secondary outcome [18] 401621 0
Incidence of adverse events (e.g. diarrhoea) for the treatment group between 19-24 months as reported in diary and/or medical records collected monthly
Timepoint [18] 401621 0
19-24 months after starting treatment, as reported in diary and/or medical records collected monthly
Secondary outcome [19] 401622 0
Incidence of serious adverse events for the treatment group between 19-24 months as reported in diary and/or medical records collected monthly
Timepoint [19] 401622 0
19-24 months after starting treatment, as reported in diary and/or medical records collected monthly
Secondary outcome [20] 401623 0
Incidence of Suspected Unexpected Serious Adverse Reaction (SUSARs) such as hospitalisations, for the treatment group between 19-24 months as reported in diary and/or medical records
Timepoint [20] 401623 0
19-24 months after starting treatment, as reported in diary and/or medical records collected monthly

Eligibility
Key inclusion criteria
- Parent/Guardian able to provide written informed consent
- Within 6 weeks of discharge from hospital for bronchiolitis
- Child aged 3-12 months at the time of consent to study
- A diagnosis of Bronchiolitis requiring a hospital admission (defined as more than 4 hours in hospital)
- Contactable for regular follow up by the research team
Minimum age
3 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any previous hospital attendance for bronchiolitis
- More than one episode of healthcare professional-diagnosed wheeze prior to index bronchiolitis episode
- Premature gestational age less than 37 weeks
- Any severe chronic condition such as cystic fibrosis, sickle cell disease, severe developmental delay, immunodeficiency, or anything that has a significant impact on the respiratory tract (such as need for non-invasive ventilation) or increases vulnerability to respiratory tract infections.
- History of clinically significant neonatal disease (e.g. neonatal pneumonia, congenital lung abnormality, neonatal chronic lung disease)
- Genetic conditions that affect the immune system (e.g. Down's syndrome/Trisomy 21)
- Current regular oral montelukast or inhaled corticosteroid therapy or inhaled salbutamol therapy
- Current regular treatment with immunomodulatory drugs (e.g oral steroids)
- Known allergy or previous intolerance to study medication.
- Currently enrolled to another RCT. (Unless prior approval is given by PI)
- Sibling of a BLIPA participant (of the same household or family)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Fully concealed through central randomisation and known only to dispensing pharmacist
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A full detailed statistical analysis plan (SAP) will be developed prior to final analysis. The purpose of the SAP is to provide details of the statistical analyses and presentation of results to be reported within the principal paper(s) of the trial. Any exploratory, post hoc or unplanned analysis will be clearly identified as such in the respective study analysis report.

The primary analysis will be conducted on the ITT population. The primary outcome of parent-reported, healthcare professional-confirmed, wheeze between 19 and 24 months will be analysed using a mixed-effect logistic regression model. The magnitude of the treatment effect will be reported as an odds ratio with a 95% confidence interval. Significance will be set at p<0.05. Should any variables of interest be identified in the scientific literature during the course of the trial their analysis will be considered exploratory and detailed in the SAP.

The primary analysis will be repeated on the compliant population, defined as those who take at least 80% of the assigned medication over the 24 months of treatment, evidenced by the parent-reported treatment diary.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2021
Actual
21/02/2022
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
31/01/2026
Actual
Sample size
Target
894
Accrual to date
26
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,VIC
Recruitment hospital [1] 20662 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 20663 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [3] 20665 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 20666 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 35452 0
4101 - South Brisbane
Recruitment postcode(s) [2] 35453 0
0810 - Tiwi
Recruitment postcode(s) [3] 35455 0
2145 - Westmead
Recruitment postcode(s) [4] 35456 0
3052 - Parkville
Recruitment outside Australia
Country [1] 24166 0
United Kingdom
State/province [1] 24166 0
London

Funding & Sponsors
Funding source category [1] 309825 0
Government body
Name [1] 309825 0
Medical Research Future Fund/NHMRC
Country [1] 309825 0
Australia
Funding source category [2] 309826 0
Government body
Name [2] 309826 0
NIHR
Country [2] 309826 0
United Kingdom
Primary sponsor type
University
Name
Queensland University of Technology
Address
2 George Street
Brisbane
Queensland
Australia 4001
Country
Australia
Secondary sponsor category [1] 310861 0
Hospital
Name [1] 310861 0
Queen Mary University of London
Address [1] 310861 0
Centre for Paediatrics, Institute of Cell and Molecular Science,
Queen Mary University of London
Mile End Road
London E1 4NS
UK
Country [1] 310861 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309568 0
Children’s Health Queensland Human Research Ethics Committee
Ethics committee address [1] 309568 0
Level 7,
Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 309568 0
Australia
Date submitted for ethics approval [1] 309568 0
08/06/2021
Approval date [1] 309568 0
28/07/2021
Ethics approval number [1] 309568 0
HREC/21/QCHQ/76619

Summary
Brief summary
Bronchiolitis is a common viral infection of the small airways of infants and some affected infants will require hospital admission. Severe bronchiolitis is a marker for greatly increased risk of developing both preschool wheeze and subsequent school age asthma. Since epidemiological studies suggest that exposure to microbial products protects against preschool wheeze, lysates of bacteria may prevent the development of wheeze after bronchiolitis, with long-term beneficial consequences.

BLIPA is a phase IIb, randomised, double blind, placebo-controlled study, investigating the efficacy superiority of bacterial lysate (Broncho Vaxom) capsules over placebo, in reducing wheeze in infants after severe bronchiolitis. The primary end point of the study is parent-reported, healthcare-professional confirmed wheeze at 19-24 months. The study aims to test bacterial lysate capsules (3.5mg over 24 months) for safety, efficacy, and to advance mechanistic understanding of its action.
Trial website
Trial related presentations / publications
Public notes
The primary sponsor for Australian sites is Queensland University of Technology
The primary sponsor for UK sites is Queen Mary University of London.
The overall PI is Prof Jonathan Grigg from the Queen Mary University of London

The sample size is inclusive of both Australian and UK participants

Contacts
Principal investigator
Name 114614 0
Prof Anne Chang
Address 114614 0
Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
62 Graham Street
South Brisbane QLD 4101
Country 114614 0
Australia
Phone 114614 0
+61 730697283
Fax 114614 0
Email 114614 0
[email protected]
Contact person for public queries
Name 114615 0
Anne Cook
Address 114615 0
Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
62 Graham Street
South Brisbane QLD 4101
Country 114615 0
Australia
Phone 114615 0
+61 730697283
Fax 114615 0
Email 114615 0
[email protected]
Contact person for scientific queries
Name 114616 0
Anne Chang
Address 114616 0
Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
62 Graham Street
South Brisbane QLD 4101
Country 114616 0
Australia
Phone 114616 0
+61 730697283
Fax 114616 0
Email 114616 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
In accordance to one of the sites ethics requirements, IPD cannot be shared


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.