Efficacy and safety of Doxycycline versus Macrolides for <i>Mycoplasma pneumoniae</i> INfectiOn in Children (DOMINO): a protocol for a multicentre, randomised, open-label, superiority trial.

Abstract

<i>Mycoplasma pneumoniae</i> (MP) is a major cause of community-acquired pneumonia in children. In East Asia, the prevalence of macrolide-resistant MP (MRMP) has surged, leading to treatment failures and prolonged illness. While doxycycline is an effective alternative, its use in young children has historically been limited due to concerns about tooth discolouration. This study aims to evaluate the efficacy and safety of doxycycline compared with azithromycin as a first-line treatment for children with pneumonia suspected of MRMP infection. This is a multicentre, randomised, open-label, parallel-group superiority trial conducted at 14 tertiary hospitals in South Korea. A total of 208 children (aged 3-17 years) with pneumonia and confirmed or suspected MP infection will be randomised 1:1 to receive either doxycycline (4 mg/kg/day in two divided doses for 7-14 days) or azithromycin (10 mg/kg on day 1, then 5 mg/kg on days 2-5) (online supplemental tables 1 and 2). Randomisation will be stratified by age (3-7 years vs 8-17 years). A standardised 'rescue therapy' protocol ensures patient safety by allowing control group patients to switch to doxycycline if no clinical improvement is observed within 48-72 hours. The primary outcome is the defervescence rate within 72 hours after randomisation. Secondary outcomes include treatment failure rate, length of hospital stay, symptom duration and adverse events. Safety assessment will specifically include tooth discolouration evaluation at Day 28, focused on children aged <8 years. Efficacy will be analysed using the intention-to-treat principle. This study has been approved by the Institutional Review Boards (IRB) of all participating centres. Written informed consent will be obtained from parents or legal guardians, and assent will be obtained from children aged 7 years and older. Results will be disseminated through peer-reviewed publications and conference presentations. NCT07306234.