Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms

Study Overview
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Brief Summary
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The purpose of this double-blind, randomized, controlled clinical trial is to investigate the effect of a three-day azithromycin treatment versus placebo treatment in children aged 1-5 years who are hospitalized due to asthma-like symptoms.

Detailed Description
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The children who are included must be have a known history with one or more previous episodes of asthmatic symptoms and is currently / have received treatment with SABA as monotherapy or SABA in combination with ICS and possibly LTRA. The primary purpose during hospitalization is to replicate the results of our previous study, where it was shown that azithromycin treatment significantly shortened the duration of the asthmatic episode. In this study, hospitalized children who provide a more diverse group than the COPSAC2010 cohort will be included. In addition, the study aims to focus on examining the individual response to treatment. The expectation is that in the future the study will be able to contribute to personal treatment based on the child's respiratory microbiome and / or immunological profile so that only the children who will benefit from the azithromycin treatment will receive it. The expectation is also that the study will contribute to an increased understanding of the influence of bacteria on asthma-like episodes in preschool children, and thus will lead to an evidence-based better treatment of these. The study hypothesis is: ● that antibiotic treatment with azithromycin compared to placebo in the patient group aged 1-5 years, known with previous episode (s) with asthma-like symptoms and is currently / have received treatment with SABA as monotherapy, or SABA in combination with ICS and possibly LTRA, will lead to a significant reduction in the symptom burden and duration of the asthmatic episode in days.

Official Title
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Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms: A Double-blinded, Randomized, Controlled Study

Conditions
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Childhood Asthma With Acute Exacerbation

Intervention / Treatment
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* Drug: Azithromycin Oral Liquid Product
* Other: Placebo mixture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous episode(s) with asthma-like symptoms and / medical treatment with SABA as mono-therapy or SABA in combination with ICS and possibly LTRA. The parent/guardian(s) agrees to admit the child and is willing to follow the procedure of the trial. The child is between 12-71 months old. Fluent Danish skills with parents / guardians. Exclusion Criteria: Known allergy to macrolide antibiotics. Known impaired liver function. Known renal impairment. Known with neurological or psychiatric diseases. Known with congenital or documented acquired QT interval. Known for clinically relevant bradycardia, cardiac arrhythmia or severe heart failure. Clinical signs of pneumonia (Objective findings, including severe tachypnoea: respiratory rate (RF)> 50 and / or Fever: temperature> 39 °C and / or C-reactive protein (CRP)> 50).

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 71 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antibiotics<br>Azithromycin (10mg/kg) administered via oral suspension for 3 consecutive days | Drug: Azithromycin Oral Liquid Product<br>* 10 mg/kg for 3 consecutive days<br>|
| Placebo Comparator: Placebo<br>Placebo with no active substance administered via oral suspension for 3 consecutive days | Other: Placebo mixture<br>* Placebo mixture containing no active substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration in days of the asthma-like episode from the start of randomization. | Number of days based on a diary. | 1-30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in symptom score. | Using a previously validated symptom scoring model based on a diary. The score range is from 0 (no symptoms) and up to 3 (depending on presence of one or more of the followings symptoms: Cough, breathlessness and wheezing). | From day 1 after randomization to completion of each randomized asthmatic episode aged 1-5 years. | 
| Effect modification in relation to the child's respiratory microbiota profile. | Airway microbiota, pathogenic bacteria and vira as measured by 16S-rRNA and whole genome sequencing. | Sample time, day 1 | 
| Effect modification in relation to the child's respiratory immunological profile. | Evaluation of immune mediator profiles (cytokine and chemokine levels) in the upper airway epithelial lining fluid. | Sample time, day 1 | 
| The length of hospitalization (days) | Determined by participants medical record. | 1-30 days | 
| Need for SABA during the asthma-like episode | Number of days based on a diary. | 1-30 days | 
| Need for oral corticosteroids (OCS) during the asthma-like episode. | Number of days based on a diary. | 1-30 days | 
| Stratification of the above analyzes. | On the basis of the presence or absence of bacteria/microbiota in the respiratory tract, based on outcomes 3, 4 and 5. | Sample time, day 1 | 
| Number of days away from daycare offers. | Number of days based on a diary. | 1-30 days | 
| Health economic gain based on treatment costs and lost earnings. lost earnings for parent / guardian (s) | The number of days home from daycare causing parent absenteeism due to illness based on this diary registration. | 1-30 days | 
| Gut microbiome profile | Occurrence, diversity and abundance of gut microbiota using 16S rRNA sequencing and whole genome sequencing. | 1-30 days | 
| Resistance profiles | Occurrence, diversity and abundance of antibiotic resistance genes as assessed by metagenome sequencing. | 1-30 days | 
| Adverse Event (AE) registration | Number of events and type of event based on a diary. | 1-30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Infections, Wheeze, Antibiotics