Bacterial Lysate In Preventing Asthma (BLIPA)

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

The goal of this clinical trial is to learn about the effects of using bacterial lysate in bronchiolitis. The main question it aims to answer are:

Does the use of bacterial lysate after bronchiolitis reduce the likelihood of preschool wheeze

Participants will take either the active medicine or a placebo for 24 months.

Study Overview

• Status: Recruiting
• Conditions: Asthma in Children; Bronchiolitis; Wheezing
• Intervention / Treatment: Drug: Placebo; Biological: Bacterial Lysate

Detailed Description

To establish whether there is superiority of oral BV (broncho vaxom) over placebo in the prevention of parent-reported, healthcare professional-confirmed, persistent wheeze between 19 and 24 months post initiation of IMP/placebo, after a hospital admission for severe bronchiolitis.

• Study Type: Interventional
• Enrollment (Anticipated): 894
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Emmanuel Adewunmi; Phone Number: 07919 659975; Email: blipa@qmul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Barts Health NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

1. Parent/Guardian able to provide written informed consent
2. Within 6 weeks of discharge from hospital following admission for bronchiolitis
3. Child aged is ≥2 weeks of age and ≤ 12 months on the date of hospital admission for Bronchiolitis
4. A diagnosis of Bronchiolitis requiring a hospital admission (defined as more than 4 hours in hospital)
5. Contactable for regular follow up by the research team

EXCLUSION CRITERIA

1. Any previous hospital attendance for bronchiolitis
2. More than one episode of healthcare professional-diagnosed wheeze prior to index bronchiolitis episode
3. Premature gestational age less than 34 weeks
4. 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.
5. History of clinically significant neonatal disease (e.g. neonatal pneumonia, congenital lung abnormality, neonatal chronic lung disease)
6. Genetic conditions that affect the immune system (e.g. Down's syndrome/Trisomy 21)
7. Current regular oral montelukast or inhaled corticosteroid therapy or inhaled salbutamol therapy
8. Current regular treatment with immunomodulatory drugs (e.g oral steroids)
9. Known allergy or previous intolerance to study medication.
10. Enrolment in another clinical trial of a medicinal product. Non-CTIMP study participation is allowed.
11. 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
Active Comparator: Intervention; Bacterial Lysate - Broncho-Vaxom (OM-85) 3.5mg granules once daily for 10 days per month for 24 months	Biological: Bacterial Lysate; Bacterial Lysate
Placebo Comparator: Placebo; Placebo - 3.5mg granules once daily for 10 days per month for 24 months	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of parent-reported, healthcare professional-confirmed wheeze between 19 and 24 months after initiation of IMP or placebo.	Occurrence of parent-reported, healthcare professional-confirmed wheeze between 19 and 24 months after initiation of IMP or placebo.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of medication	Prescription for more than one salbutamol inhaler	24 months
Asthma or Wheeze Diagnosis	Active wheeze diagnosis on primary care record Asthma diagnosis on primary care record Parental report of wheeze episode - time in days to first episode of wheeze from initiation of IMP or placebo	24 months
Unscheduled Medical attendances	Number of unscheduled medical attendances for wheeze Number of hospital admissions for wheeze Number of days admitted to hospital for wheeze Number of unscheduled medical attendances for any lower respiratory symptoms	24 months
Number of courses of oral steroids	Number of courses of systemic corticosteroids (within the 24 months post initiation of IMP or placebo) Number of courses of oral corticosteroids for wheeze	24 months
Montelukast use	Prescription of regular oral montelukast (yes/no)	24 months
Number of courses of antibiotics	Number of courses of antibiotics	24 months
Eczema diagnosis	Eczema (yes/no) Eczema confirmed by U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis.	24 months
Safety and Tolerability	Number of AE/SAE/SUSAR events across 0-24 months and 19-24 months	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in children between treatment with BV granules or placebo in parent-reported clinical outcome measures between 0-24 months.	Time in days to first episode of wheeze from initiation of IMP or placebo Number of unscheduled medical attendances for wheeze Number of hospital admissions for wheeze Number of days admitted to hospital for wheeze Number of unscheduled medical attendances for any lower respiratory symptoms Number of courses of systemic corticosteroids (within the 24 months post initiation of IMP or placebo) Number of courses of oral corticosteroids for wheeze Number of courses of antibiotics This will be a combination outcome of the following factors. Prescription of regular oral montelukast (yes/no)	24 months
Assess compliance with the medications	Combination outcome combining the following. Compliance with medication assessed from monthly questionnaires completed by parents and guardians. The effect of oral BV on parent-reported, healthcare-professional confirmed wheeze in the stratum of patients that have met compliance as defined as 80% of capsules taken across the whole 24 months.	24 months
Parents and healthcare professionals' self-assessment of blinding	Parent prediction: BV or placebo Healthcare professional prediction: BV or placebo	24 months
Markers of atopy and BV function	Blood serum total and specific IgE and blood eosinophil	24 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Collaborators: King's College London; University of Southampton; University of Edinburgh; Menzies School of Health Research; University of Aberdeen

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: asthma; placebo; allergy; bacterial lysate; wheeze
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Bronchitis; Asthma; Bronchiolitis; Respiratory Sounds; Physiological Effects of Drugs; Immunologic Factors; 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
• IPD Plan Description: This will be discussed at TSC and changed if felt approapriate

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