Oral bacterial lysate treatment for prevention of recurrent wheeze following severe bronchiolitis: protocol for an international multicentre randomised, placebo-controlled trial (BLIPA)

Abstract Background Bronchiolitis is a common condition caused by a viral acute lower respiratory infection (ALRI) in infants. Severe bronchiolitis requiring hospitalisation is associated with increased risk of preschool wheeze and school-age asthma. Early exposure to microbial products modulating immune system development may help prevent later wheeze. Thus, this study evaluates whether an oral bacterial lysate after bronchiolitis hospitalisation reduces subsequent wheezing episodes. Methods This international multicentre, randomised, double-blind, placebo-controlled trial tests bacterial lysate (OM85-BV; Broncho-Vaxom®) in infants after hospitalisation for bronchiolitis. Safety and efficacy will be assessed, and a subset will undergo exploratory mechanistic analyses. For 12–24 months post-discharge, parents/guardians will give one capsule of OM85-BV or placebo daily for 10 consecutive days each month. Results The primary endpoint is the number of parent/guardian-reported wheeze episodes 12-months after starting OM85-BV or placebo. Secondary outcomes at 12 or 24-months follow-up include clinical outcomes, parent-proxy quality-of-life scores, incidence of atopy, recurrent wheeze needing asthma medication, wheeze-related hospitalisations, number of ALRI episodes, and mechanistic data on systemic immune pathways and nasopharyngeal and gut microbiota. Conclusions This international multicentre study will determine whether oral OM85-BV given for 10 consecutive days each month for 12–24 months reduces parent/guardian-reported recurrent wheeze episodes post-hospitalisation for bronchiolitis. Trial registration (4) AZNCTR ACTRN12621001556831 (5/10/2021) and clinicaltrials.gov NCT05064631 (20/08/2020). Prospectively Registered. Approval to use the IMP in this clinical trial was provided by the Australian Government Therapeutic Goods Agency under the clinical trials notification scheme (TGA CTN: CT-2021-CTN-02639-1). Impact Our study addresses a large unmet clinical need and research gap related to reducing recurrent wheeze in infants post-hospitalisation for bronchiolitis. If our hypothesis is correct, this study may lead to an implementable intervention to improve health outcomes by reducing recurrent wheeze episodes in infants and young children. Reductions in recurrent wheeze might also reduce the incidence of childhood asthma and improve the lung health trajectories of children hospitalised with severe bronchiolitis.