Enhancing Lung Health in Children with Structural Damage and Malformations: Trial Protocol for a Randomized Controlled Trial of Azithromycin for Airway Infection Prevention

Background Children with early-onset structural lung damage or lung and airway malformations – congenital or acquired – are highly susceptible to recurrent respiratory tract infections, leading to frequent hospitalizations, impaired lung function, and reduced quality of life. Although azithromycin maintenance therapy is commonly used in this population, robust clinical evidence supporting its efficacy is lacking. Objectives The primary aim of this trial is to evaluate the efficacy of azithromycin maintenance therapy in reducing respiratory infections among young children with structural lung damage or lung and airway malformations. Secondary objectives are to assess the efficacy of azithromycin on lung function, daily respiratory symptoms, quality of life, as well as the safety of long-term azithromycin use in this age group. Methods This is a national, multicentre, double-blind, placebo-controlled randomized clinical trial conducted across three specialized pediatric pulmonology centres in Denmark. A total of 150 children aged 0–72 months with structural lung damage or lung or airway malformations confirmed by bronchoscopy or radiology will be enrolled. Participants will be randomized 1:1 to receive either oral azithromycin (10 mg·kg −1 ) or placebo three times weekly for 6 months during the winter season. Ethics and disseminations The trial has been approved by the European Medical Agency (EMA). It is expected to provide high-quality evidence on efficacy and safety of azithromycin maintenance therapy in a vulnerable pediatric population with rare respiratory conditions. Positive findings will inform clinical guidelines and help enhance lung health; conversely, if treatment proves ineffective, results may support efforts to reduce unnecessary antibiotic use.