A randomised, double-blind, parallel group, placebo controlled, trial of Bactek for the prevention of lower respiratory tract infections in preterm infants (BALLOON)

Research question Does treatment with BactekTM sublingual spray (MV-130) decrease unscheduled visits to health care professionals for lower respiratory tract infections (LRTIs), when compared to placebo? Background Significant proportion of infants born at <30 weeks’ gestation develop lung disease during the neonatal period thus are at risk of significant lung disease in child- and adult-hood. At discharge from the neonatal unit, pre-existing lung disease is exacerbated by frequent respiratory viral infections requiring medical assessment. The therapeutic options besides anti-RSV prophylaxis are limited. One approach is to use inactivated bacterial vaccines such as Bactek (MV-130) to provide protection via activation of innate and adaptive immunity. Aims and objectives Primary Objective: • To investigate if Bactek, when compared to placebo, decreases health professional diagnosed LRTIs (after unscheduled visits to general practitioners (GPs), A&E and hospital admissions) between term-equivalent 37 weeks’ gestation and 1 year of corrected age. Secondary Objectives: • Is Bactek superior to placebo in preventing parent-reported, health professional confirmed, wheezing from 37 weeks’ corrected gestation to one year of corrected age in infants born at <30 weeks’ gestational age • Compare respiratory medication use including inhalers (bronchodilators, inhaled corticosteroids), antibiotics and systemic corticosteroids between the two groups • Establish effects of LRTI on the family, including time missed from work and/or nursery time missed for the infants • Explore differential intervention effects by gestational age, anti-RSV prophylaxis, and centre • Assess safety Mechanistic objectives: • Serially assess effect of Bactek on the infants’ adaptive immune and its modulation by Bactek including the effects on Th1/Th2/Th17 and Treg phenotypes • Establish respiratory viruses associated with LRTIs in the two groups to identify impact of treatment. Assess modulation of virus-specific antibody responses by Bactek • Serially assess infant’s airway resistance and compliance using oscillometry to identify any improvement after Bactek intervention Methods We will conduct a randomised, double-blind, two-stage placebo-controlled trial. Eligible infants will be ex-preterm (born at <30 weeks’ gestation) and approaching discharge from their initial neonatal stay. They will be randomised to receive Bactek or matching placebo for treatment from term-equivalent 37 weeks’ corrected gestation to 1 year corrected age. Parents will be reminded daily to administer treatment and record symptoms on a Trial App. They will be contacted each month by the research nurse to report any respiratory symptoms, medication use, or unscheduled contact with health professionals. We require 542 infants, with interim analysis conducted after 346 infants are recruited. Timelines Project start date is January 2024 with patient enrolled from July 2024. Pilot will be reported after 9 months recruitment and interim analyses after for 18 months recruitment. Enrolment will complete in June 2026, and follow-up in August 2027 with reporting completed by January 2028. Iimpact and dissemination We will disseminate our results via international peer-reviewed high-ranking journals and national/international conferences and to the parents via the trial website. The treatment will be simple to establish as these infants are generally discharged after a prolonged stay in the neonatal unit.