Enhancing Lung Health in Kids with structural Lung Damage and Malformations: a randomized controlled trial on Azithromycin (AZI) for Airway Infection Prevention

The primary objective is to determine the efficacy of 6 months of maintenance treatment with **azithromycin** on the incidence of **respiratory exacerbations** in subjects with **structural lung damage** or **congenital lung and airway malformations**, aged 0-72 months. This objective addresses a clinically significant need to prevent recurrent respiratory complications in pediatric patients with underlying pulmonary anatomical abnormalities, including **tracheomalacia**, **cystic lung malformations**, post-vascular ring with central airway compression, **lobar hyperinflation syndrome**, **bronchopulmonary dysplasia**, **bronchiectasis**, and **chronic atelectasis**. The secondary objective is to determine the efficacy of 6 months of maintenance treatment with azithromycin on the severity of respiratory exacerbations in the same patient population. This evaluation is clinically relevant as it assesses whether prophylactic macrolide therapy can reduce not only the frequency but also the intensity of exacerbations, potentially decreasing hospitalizations, need for additional antimicrobial therapy, and overall disease burden in this vulnerable pediatric cohort.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of **pediatric patients** aged **0 to 72 months** (birth to 6 years), including both **male** and **female** subjects. This trial involved a **vulnerable population** and specifically recruited **infants and children** with **radiologically** or **bronchoscopically** verified **structural lung damage** or **congenital lung and airway malformations**. The targeted conditions included **tracheomalacia**, **cystic lung malformations**, post-vascular ring with **central airway compression**, **lobar hyperinflation syndrome**, **bronchopulmonary dysplasia**, **bronchiectasis**, and **chronic atelectasis**. Participants were selected from those affiliated as outpatients with specialized pediatric pulmonology centers and were required to be at risk of or have already documented **respiratory infections** requiring **antibiotic** treatment. Parental written informed consent was mandatory for participation. No specific information regarding lifestyle considerations such as diet, physical activity, or habits was provided by the sponsor.

This is a randomized controlled trial evaluating the efficacy of maintenance treatment with **azithromycin** in pediatric subjects with structural lung damage or congenital lung and airway malformations. The study investigates multiple conditions including **tracheomalacia**, **cystic lung malformations**, post-vascular ring with central airway compression, lobar hyperinflation syndrome, **bronchopulmonary dysplasia**, **bronchiectasis**, and chronic atelectasis. The trial is designed as a phase IV clinical trial utilizing an antibiotic for maintenance therapy purposes. Participants will be randomized to receive either azithromycin oral suspension or placebo for azithromycin, with the active treatment administered at a maximum daily dose of 30 mg/kg and a maximum total dose of 100 mg/kg over the treatment period.

The primary objective is to determine the efficacy of 6 months of maintenance treatment with azithromycin on the incidence of **respiratory exacerbations** in subjects aged 0-72 months with structural lung damage or congenital lung and airway malformations. The primary endpoint focuses on the difference in the number of respiratory exacerbations between treatment groups during the intervention period. Secondary endpoints include the difference in duration of exacerbations, number of hospital admissions, and duration of hospital admissions between the treatment groups during the intervention period. The maximum treatment period is 6 months, during which participants will receive the assigned intervention.

Eligible participants must have radiologically or bronchoscopically verified structural lung damage or congenital lung and airway malformations, be affiliated as outpatients with one of the specialized pediatric pulmonology centers, and be at risk of or have already documented respiratory infections requiring antibiotics. The age range for inclusion is 0-72 months. Parents must provide written informed consent for their child to participate in the trial according to local regulations. The trial is expected to commence recruitment in September 2025 and is estimated to conclude in May 2028, representing an overall trial duration of approximately 32 months.

Participant involvement will span the 6-month intervention period during which study medication or placebo will be administered. Study visits will include a screening visit to verify eligibility criteria and obtain informed consent, followed by scheduled follow-up visits throughout the intervention period to monitor treatment efficacy, assess respiratory exacerbations, record hospital admissions, and evaluate safety parameters. An end-of-study visit will be conducted upon completion of the 6-month treatment period to perform final assessments and collect concluding data. Conditions that may lead to early termination from the study would typically include withdrawal of parental consent, development of significant adverse events, protocol violations, or other safety concerns as determined by the investigator, though specific early termination criteria are not detailed in the available protocol information.

The experimental treatment in this clinical trial consists of **azithromycin** administered as **ZITHROMAX 40 mg/ml powder for oral suspension**. The **active substance** is azithromycin, a **macrolide antibiotic** of chemical origin. The **pharmaceutical form** is an oral suspension prepared from powder. The medication is administered via the **oral route**. The **dosage** is calculated based on body weight, with a **maximum daily dose** of 30 mg/kg and a **maximum total dose** of 100 mg/kg over the treatment period. The **treatment duration** is 6 months of maintenance therapy. The product is manufactured by PFIZER OY and holds marketing authorization in Finland under authorization number 11615. The **ATC code** is J01FA10.

The **comparator treatment** consists of a **placebo** for azithromycin. The placebo is designed to match the experimental medication to maintain blinding in this randomized controlled trial. Specific details regarding the pharmaceutical form, composition, and administration characteristics of the placebo are not provided in the available documentation. The placebo is administered following the same schedule and route as the active treatment to ensure consistency in trial methodology.

The trial investigates the **efficacy** of the maintenance treatment regimen in preventing respiratory exacerbations in pediatric subjects aged 0-72 months with **structural lung damage** or **congenital lung and airway malformations**. Both the experimental medication and placebo are prepared and dispensed according to pharmaceutical standards, with appropriate certification maintained by the regional pharmacy authority to ensure quality control and compliance throughout the study period.

Efficacy will be assessed through the evaluation of respiratory exacerbations in subjects with structural lung damage or congenital lung and airway malformations during the intervention period. The primary endpoint is the difference in the number of respiratory exacerbations between the treatment groups receiving azithromycin maintenance therapy and placebo over the 6-month intervention period. Secondary endpoints include the difference in duration of exacerbations between the treatment groups, the difference in number of hospital admissions between the treatment groups, and the difference in duration of hospital admissions between the treatment groups during the intervention period. These parameters will be used to determine the efficacy of azithromycin in preventing airway infections and reducing disease burden in the study population aged 0-72 months.