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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
20/12/2024
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 up to 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 up to 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
Rate of parent reported wheeze post IMP/placebo initiation. Where wheeze is defined as episodes of wheeze lasting at least 24 hours. Second episodes of wheeze will be considered present if there is a 7/7 break between episodes where data is available, where data is not available an independent clinician will support in defining the episodes with a max of 2 episodes per month.
Timepoint [1] 329142 0
At 12 months
Secondary outcome [1] 401604 0
Number of episodes where salbutamol was used, as reported by the parent(s)/carer(s), collected monthly after starting treatment.
Timepoint [1] 401604 0
12 and 24 months after starting treatment
Secondary outcome [2] 401605 0
Proportion of participants with 'ever-wheeze' recorded on primary care or hospital records, post commencement of treatment.
Timepoint [2] 401605 0
12 and 24 months after starting treatment
Secondary outcome [3] 401606 0
Asthma diagnosis (defined as >1 episode of salbutamol-responsive wheeze) as reported by medical records or parents, collected monthly from commencement of treatment.
Timepoint [3] 401606 0
12 and 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 collected monthly from parents (and checked with medical records when possible) from commencement of treatment.
Timepoint [5] 401608 0
12 and 24 months after starting treatment
Secondary outcome [6] 401609 0
Number of hospital admissions for wheeze collected from medical records from commencement of treatment.
Timepoint [6] 401609 0
12 and 24 months after starting treatment
Secondary outcome [7] 401610 0
Number of days admitted to hospital for wheeze collected from medical records, from commencement of treatment.
Timepoint [7] 401610 0
12 and 24 months after starting treatment
Secondary outcome [8] 401611 0
Number of unscheduled medical attendances for any lower respiratory symptoms after starting treatment, collected from parents through e-records and/or phone calls
Timepoint [8] 401611 0
12 and 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] 401614 0
Number of courses of antibiotics for wheeze after starting treatment using using diary reports and/or medical records.
Timepoint [10] 401614 0
12 and 24 months after starting treatment
Secondary outcome [11] 401616 0
Parent reported eczema after starting treatment.
Timepoint [11] 401616 0
12 and 24 months after starting treatment
Secondary outcome [12] 401617 0
Presence of Eczema confirmed by U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis.

Timepoint [12] 401617 0
12 and 24 months after starting treatment
Secondary outcome [13] 401618 0
Incidence of adverse events for the treatment group between 0-24 months using using diary reports and/or medical records
Timepoint [13] 401618 0
0-24 months after starting treatment, using diary reports and/or medical records
Secondary outcome [14] 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 [14] 401619 0
0-24 months after starting treatment, using diary reports collected monthly
Secondary outcome [15] 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 [15] 401620 0
0-24 months after starting treatment, as reported in diary and/or medical records collected monthly
Secondary outcome [16] 401621 0
Incidence of adverse events (e.g. diarrhoea) for the treatment groups as reported in diary and/or medical records collected monthly.
Timepoint [16] 401621 0
12 and 24 months after starting treatment
Secondary outcome [17] 401622 0
Incidence of serious adverse events for the treatment groups as reported in diary and/or medical records collected monthly.
Timepoint [17] 401622 0
12-24 months after starting treatment
Secondary outcome [18] 441600 0
Occurence of doctor-diagnosed food allergy as reported by parents or e-records, post commencement of treatment.
Timepoint [18] 441600 0
24 months post commencement of treatment
Secondary outcome [19] 441601 0
Occurence of doctor-diagnosed food allergy as reported by parents or e-records, post commencement of treatment.
Timepoint [19] 441601 0
12 and 24 months post commencement of treatment
Secondary outcome [20] 441602 0
Rate of parent reported wheeze post IMP/placebo initiation collected monthly. Wheeze is defined as episodes of wheeze lasting at least 24 hours. Second episodes of wheeze will be considered present if there is a 7/7 break between episodes where data is available, where data is not available an independent clinician will support in defining the episodes with a max of 2 episodes per month.
Timepoint [20] 441602 0
12 and 24 months post commencement of treatment
Secondary outcome [21] 441603 0
Rate of parent reported wheeze post IMP/placebo initiation collected monthly. Wheeze is defined as episodes of wheeze lasting at least 24 hours. Second episodes of wheeze will be considered present if there is a 7/7 break between episodes where data is available, where data is not available an independent clinician will support in defining the episodes with a max of 2 episodes per month.
Timepoint [21] 441603 0
24 months
Secondary outcome [22] 441604 0
Quality of life (Warwick Child Health and Morbidity Profile)
Timepoint [22] 441604 0
24 months
Secondary outcome [23] 441605 0
Quality of life (Warwick Child Health and Morbidity Profile)
Timepoint [23] 441605 0
12 and 24 months

Eligibility
Key inclusion criteria
- Parent/Guardian able to provide written informed consent
- Within 6 weeks of discharge from hospital for bronchiolitis
- Child aged 2 weeks to 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
2 Weeks
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 34 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 rate of parent-reported wheeze (from start of treatment to 12 months post commencement of trearment) will be analysed using a mixed-effect logistic regression model. The magnitude of the treatment effect will be reported as an rate ratio with a 95% confidence interval. The variable length of follow-up per participant will be accounted for using an offset term. 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 70% of the assigned medication over the 12 months of treatment, evidenced by the parent-reported treatment diary.

We will also undertake the above analysis at the 24-month timepoint from commencement of treatment,


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2021
Actual
21/02/2022
Date of last participant enrolment
Anticipated
31/05/2025
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
178
Accrual to date
150
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
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
Trial website
Trial related presentations / publications
Public notes

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
kidslungresearch@qut.edu.au
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
kidslungresearch@qut.edu.au
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
kidslungresearch@qut.edu.au

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.