{
  "abstract": "Introduction A significant proportion of infants born at ≤29+6 weeks’ gestation develop lung disease during the neonatal period, thus putting them at risk of developing prematurity-associated lung disease in childhood and adulthood. After discharge from the neonatal unit, pre-existing lung disease in preterm-born infants is exacerbated by (often frequent) respiratory viral infections requiring greater health utilisation, including hospital admissions, than their term-born equivalents. Opportunities to prevent viral infections in infancy are largely limited to anti-respiratory syncytial virus (RSV) antibody prophylaxis and recently maternal RSV immunisation, but in term-born infants, trained immunity-based vaccines such as Bactek (MV130, Inmunotek, Spain) are increasingly used. Bactek provides a promising therapeutic avenue for preterm-born infants to target postdischarge respiratory viral infection in this vulnerable group of infants. The BALLOON study aims to assess this treatment in a very/extremely preterm-born population and determine if treatment with the trained immunity-based vaccine Bactek decreases the risk of unscheduled visits to healthcare professionals for lower respiratory tract infections, when compared with placebo. Included infants are born at ≤29+6 weeks’ gestation and treated daily from term-equivalent (37–43 weeks’ postmenstrual age, PMA) or from discharge, if earlier, up to 1 year of corrected age.Methods and analysis 542 infants are being recruited prior to discharge by neonatal units in the UK. They are being randomised to receive Bactek or placebo, once daily dose of 2 sprays (each 0.1 mL) of IMP (300 Formazin Turbidity Units), from 37 to 43 weeks’ PMA or discharge if earlier up to 1 year of corrected age. The primary objective is to assess if sublingual Bactek spray decreases the risk of health professional diagnosed lower respiratory tract infections (LRTIs) (unscheduled visits to general practitioners, accident and emergency departments and hospital admissions) between enrolment and 1 year of corrected age. Secondary outcomes include the number of parent-reported, health professional-confirmed unscheduled visits for LRTIs, the time to first parent-reported, health professional-confirmed unscheduled visit for LRTI, parent-reported wheeze episodes (identification aided by WheezeScan (Omron, Japan)), parent-reported use of respiratory medications, growth (weight, length and head circumference), parent(s)/guardian(s) reported time missed from work and/or nursery time missed for the infant and volume of adverse reactions. Viruses associated with LRTIs will also be identified.Ethics and dissemination Ethics permission has been granted by the Wales Research Ethics Committee 3 (Ref 24/WA/0181), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (CTA reference 21323/0063/001-0004). The study is registered on ISRCTN ( ISRCTN14019493). Findings will be disseminated via national and international peer-reviewed journals, and conferences. Oversight of the study is being provided by an Independent Data Monitoring Committee and an independent Trial Steering Committee (TSC). The Trial Management Group (TMG) meets every month.Trial registration number ISRCTN14019493.",
  "authors": [
    {
      "affiliations": [
        "Department of Child Health, Cardiff University, Cardiff, UK"
      ],
      "name": "Sarah Joanne Kotecha"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "John Lowe"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "David Gillespie"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "Mahuampi Perez-Alijas"
    },
    {
      "affiliations": [
        "Department of Child Health, Cardiff University School of Medicine, Cardiff, UK"
      ],
      "name": "Ali F Aboklaish"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "Tarirai Lincoln Mahachi"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "Oliver Sebastian Cumming"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "Debbie Harris"
    },
    {
      "affiliations": [
        "Neonatal Unit, University Hospitals of Leicester NHS Trust, Leicester, UK"
      ],
      "name": "Marie Hubbard"
    },
    {
      "affiliations": [
        "Centre for Trials Research, University of Cardiff, Cardiff, UK"
      ],
      "name": "Emma Thomas-Jones"
    },
    {
      "affiliations": [
        "University Hospital of Wales, Cardiff, Wales, UK"
      ],
      "name": "Tim Jones"
    },
    {
      "affiliations": [
        "Department of Child Health, Cardiff University School of Medicine, Cardiff, UK"
      ],
      "name": "Kirstin Ladell"
    },
    {
      "affiliations": [
        "University Hospital of Wales, Cardiff, Wales, UK"
      ],
      "name": "Catherine Moore"
    },
    {
      "affiliations": [
        "Cardiff University, Cardiff, UK"
      ],
      "name": "Ian Humpreys"
    },
    {
      "affiliations": [
        "Paediatric Respiratory, Queen Mary University London, London, UK"
      ],
      "name": "Jonathan Grigg"
    },
    {
      "affiliations": [
        "Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"
      ],
      "name": "Janet Berrington"
    },
    {
      "affiliations": [
        "Department of Child Health, Cardiff University School of Medicine, Cardiff, UK"
      ],
      "name": "Sailesh Kotecha"
    }
  ],
  "title": "Randomised, double-blind, parallel group, placebo-controlled, trial of Bactek for the prevention of lower respiratory tract infections in preterm infants in the UK: BALLOON study – study protocol",
  "uid": "a93c6609-b22e-598d-8c3a-fd682286efbb"
}