Bacterial Lysate In Preventing Asthma (BLIPA)

Oral Bacterial Lysate to Prevent Persistent Wheeze in Infants After Severe Bronchiolitis; a Randomised Placebo-controlled Trial

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 2b, 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 to establish whether there is superiority of oral Broncho-Vaxom over placebo in reducing the number of parent-reported wheeze episodes by 12 months post IMP/placebo initiation. The study aims to test bacterial lysate capsules (3.5mg over 12-24 months) for safety, efficacy, and to advance mechanistic understanding of its action.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Pediatric Respiratory Diseases; Wheezing
• Intervention / Treatment: Drug: Bacterial Lysate

Detailed Description

The BLIPA study aims to investigate the following research questions:

1. In children hospitalised with bronchiolitis, does Oral Broncho-Vaxom reduce incidence of parent-reported wheeze during 12 months post IMP initiation after a hospital admission for bronchiolitis.
2. Does oral BV reduces the risk of wheeze after bronchiolitis by modulating T cell and Dendritic cells (DC) maturation and altering the gut and airway microbiota. (mechanistic hypothesis)

The BLIPA study will combine the results of two multi-centre, randomised trials with similar but separate protocols: BLIPA-United Kingdom (UK), with recruitment in London, Southampton, Cheshire and Aberdeen and BLIPA-Australia, with recruitment in Brisbane, Gold Coast, Melbourne, Darwin and Sydney.

BLIPA-UK is funded in the UK by the NIHR (National Institute for Health and Care Research). BLIPA-Australia is funded in Australia by the International Clinical Trial Collaboration (ICTC). ICTC supports Australian researchers to conduct clinical trial research in collaboration with international researchers.

The total study duration is 74 months. The primary clinical objective is to recruit a population of eligible participants, to randomise them to oral Broncho Vaxom (3.5mg) or placebo, to be taken daily for 10 days a month over 12-24 months, follow up for 12-24 months and compare primary and secondary outcomes between trial arms. Parents or guardians of children, clinicians involved in their care and trial staff will be blinded to the treatment arm. Recruitment will be for 18 months and children's outcomes will be assessed for 24 months following initiation of Investigational Medicinal Product (IMP) or placebo.

Within six weeks of hospital discharge following admission for bronchiolitis, parents or guardians can consent to their child partaking in the study, baseline data is collected, the child is randomised, and the IMP or placebo is initiated (12 months' supply). From the point of treatment initiation, children are followed up for 12-24 months, the same length as the treatment period. There will be at least one scheduled face to face visit at 12 months to dispense a further year's supply of IMP or placebo.

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 1FR
    • Royal London Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Parent/Guardian able to provide written informed consent
• Within 6 weeks of discharge from hospital for bronchiolitis
• Child aged ≥2 weeks and ≤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

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 Randomised Clinical Trial. (Unless prior approval is given by Principal Investigator)
• Sibling of a BLIPA participant (of the same household or family)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active intervention; Oral Broncho-Vaxom (3.5mg) administered daily for 10 days per month for 12-24 months	Drug: Bacterial Lysate; Bacterial lysate medicines are made from bacterial cells that are broken down and are intended to stimulate the immune system.; Other Names: Broncho Vaxom
Placebo Comparator: Placebo control; Matched placebo administered daily for 10 days per month for 12-24 months	Drug: Bacterial Lysate; Bacterial lysate medicines are made from bacterial cells that are broken down and are intended to stimulate the immune system.; Other Names: Broncho Vaxom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of a wheeze episodes by 12 months	To establish whether there is superiority of oral Broncho-Vaxom over placebo in the reduction of parent reported wheeze episodes by 12 months post IMP/placebo initiation	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) for the treatment group between 0-24 months	Number of AEs across 0-24 months	0-24 months
Incidence of serious adverse events (SAEs) for the treatment group between 0-24 months	Number of SAEs across 0-24 months	0-24 months
Incidence of Suspected unexpected serious adverse reactions (SUSARs) for the treatment group between 0-24 months	Number of SUSARs across 0-24 months	0-24 months
To establish whether there is a difference between treatment with Broncho-Vaxom or placebo in healthcare professional confirmed wheeze episodes by 12 months post IMP initiation.	Wheeze confirmed via one of the following: Prescription for more than one salbutamol inhaler coded in primary care record between 0-12 months post IMP/placebo initiation.; Active wheeze code in primary care records between 0-12 months post IMP/placebo initiation.; Asthma diagnosis code in primary care records between 0-12 months post IMP/placebo initiation.	12 months
Occurrence of hospital admissions for wheeze-related illness by 12 months.	Occurrence of hospital admissions for wheeze-related illness by 12 months.	12 months
Occurrence of unscheduled medical attendance for wheeze-related illness by 12 months	Occurrence of unscheduled medical attendance for wheeze-related illness (rate[episodes per child/month] and yes/no).	12 months
Presence of wheeze diagnosis by 12 months	Presence of wheeze diagnosis by 12 months	12 months
Time to first wheeze episode by 12 months	Time to first wheeze episode by 12 months	0-12 months
Duration of wheeze by 12 months	Duration of wheeze by 12 months	12 months
Development of eczema by 12 months	Development of eczema by 12 months confirmed by parent report at study follow ups (parent reported outcome)	12 months
Development of Dr-diagnosed food allergy by 12 months	Development of Dr-diagnosed food allergy by 12 months	12 months
Occurrence of all-cause acute respiratory infection by 12 months	Occurrence of all-cause acute respiratory infection by 12 months	12 months
Hospital admissions for respiratory related illness (rate[episodes per child-month] and yes/no) by 12 months	Hospital admissions for respiratory related illness (rate[episodes per child-month] and yes/no) by 12 months	12 months
Quality of life confirmed by Warwick Child Health and Morbidity by 12 months	Quality of life confirmed by Warwick Child Health and Morbidity by 12 months	12 months
Number of courses of oral corticosteroids for wheeze by 12 months	Number of courses of oral corticosteroids for wheeze by 12 months	12 months
Incidence of adverse events (AEs) for the treatment group by 12 months	Number of AEs by 12 months	12 months
Incidence of serious adverse events (SAEs) for the treatment group by 12 months	Number of SAEs by 12 months	12 months
Incidence of Suspected unexpected serious adverse reactions (SUSARs) for the treatment group by 12 months	Number of SUSARs by 12 months	12 months

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: Queensland University of Technology
• Investigators: Study Chair: Jonathan Grigg, Prof. Dr, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Actual): June 13, 2024
• Study Completion (Actual): June 13, 2024

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Bronchiolitis; Wheeze; Asthma in childhood; Bacterial lysate
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Signs and Symptoms, Respiratory; Bronchitis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Respiratory Tract Infections; Bronchiolitis; Respiratory Sounds; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Broncho-Vaxom
• Other Study ID Numbers: 295882; 2021-000628-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No