Evaluation of Azithromycin Versus Placebo in Hospitalized Pediatric Patients with Asthma-Like Symptoms: A Double-Blind, Randomized, Controlled Trial

The primary objective of this study is to evaluate the effect of a three-day treatment with **azithromycin** compared to placebo in children aged 1-5 years who are hospitalized due to asthma-like symptoms. The aim is to replicate previous findings that demonstrated a significant reduction in the duration of asthmatic episodes with azithromycin treatment. This study will include a more diverse group of hospitalized children than previous cohorts, enhancing the generalizability of the results. Clinically, this is relevant as it may provide evidence for a more effective management strategy for childhood asthma, potentially reducing hospital stays and improving patient outcomes.

The secondary objectives focus on examining individual responses to treatment, with the expectation that the study will contribute to personalized treatment strategies based on the child's respiratory microbiome and immunological profile. This could ensure that only children who are likely to benefit from azithromycin receive it. Additionally, the study aims to enhance understanding of the role of bacteria in asthma-like episodes in preschool children, potentially leading to evidence-based improvements in treatment approaches.

The clinical trial focuses on **childhood asthma** and involves a study population of children aged 1 to 5 years who are hospitalized due to asthma-like symptoms. The trial includes both male and female participants, ensuring a diverse representation of the pediatric population. The sponsor has not provided the total number of participants. The selection criteria for the trial population include children who have experienced previous episodes of asthma-like symptoms and have received medical treatment with short-acting beta-agonists (SABA) as monotherapy or in combination with inhaled corticosteroids (ICS) and possibly leukotriene receptor antagonists (LTRA). Participants are required to have fluent Danish-speaking parents or guardians who agree to the trial procedures. The study does not specifically target a vulnerable population, and no particular lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed to evaluate the efficacy of **azithromycin** in treating hospitalized children aged 1-5 years with asthma-like symptoms. This study is a **randomized**, **double-blind**, and **controlled** trial, aiming to compare a three-day treatment of azithromycin against a placebo. The trial is set to commence recruitment on October 16, 2024, and is expected to conclude by November 16, 2028. Participants will be involved in the study for a maximum of three days, corresponding to the treatment period of azithromycin.

The trial will include several study visits, beginning with a screening visit to assess eligibility based on criteria such as previous episodes of asthma-like symptoms and age between 12-71 months. Following randomization, participants will undergo daily assessments to monitor the duration of the asthma-like episode, changes in symptom scores, and any need for additional medications such as short-acting beta-agonists (SABA) or oral corticosteroids (OCS). The primary endpoint is the duration of the asthma-like episode from the start of randomization, while secondary endpoints include changes in symptom scores, length of hospitalization, and health economic assessments.

Participants will be required to attend follow-up visits to evaluate the treatment's impact on their symptoms and overall health. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted. Conditions that may lead to early termination from the study include non-compliance with the trial protocol or withdrawal of consent by the parent or guardian. The trial's design ensures that all participants receive comprehensive monitoring and care throughout their involvement.

The clinical trial involves the administration of **Azithromycin**, a macrolide antibiotic, as the primary experimental medication. Azithromycin is provided in a pharmaceutical form identified as PHF00230MIG, with a maximum daily dose of 500 mg and a total maximum dose of 500 mg over a treatment period of three days. The medication is administered orally. The trial aims to evaluate the efficacy of Azithromycin in treating children aged 1-5 years hospitalized with asthma-like symptoms. Compliance with the dosing schedule is monitored throughout the trial.

In addition to Azithromycin, the trial includes several non-experimental treatments. **Banana Flavour** is used as a flavouring agent in the form of an oral suspension. It is administered orally, with no specified maximum daily or total dose, and is used for a maximum treatment period of one day. **Xanthum Gum** is provided in cream form, also administered orally, with similar dosing parameters as Banana Flavour. **Sucrose** is included as a powder and solvent for oral solution, administered orally with no specified dosing limits, and used for a maximum of one day. **Hydroxypropyl Cellulose LF** is provided as a dispersible tablet, administered orally, with no specified dosing limits, and used for a maximum of one day. **Sodium Phosphate Dodecahydrate** is included as an oral solution, administered orally, with no specified dosing limits, and used for a maximum of one day. These non-experimental treatments serve as comparators or placebos to evaluate the primary objective of the trial.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the duration, measured in days, of the asthma-like episode from the start of randomization. This will provide a direct measure of the treatment's impact on the length of the asthmatic episode in children aged 1-5 years who are hospitalized with asthma-like symptoms.

Secondary endpoints include several parameters to evaluate the broader impact of the treatment. These are: change in symptom score from day 1 after randomization to the completion of each asthmatic episode, assessed using a previously validated symptom scoring model based on a diary; the length of hospitalization; the need for short-acting beta-agonists (SABA) during the episode; the need for oral corticosteroids (OCS); stratification of the above analyses based on the presence or absence of bacteria in the airways; percentage of days away from daycare offers and/or work for parents/guardians; and assessment of the health economic gain based on treatment costs and lost earnings for parents/guardians.

The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's effectiveness. The use of validated scales and models will ensure the reliability and accuracy of the data collected. The trial aims to explore the potential of **Azithromycin** in reducing the duration and severity of asthma exacerbations in the specified pediatric population.