Childhood Asthma With Acute Exacerbation
Conditions
Keywords
Asthma, Infections, Wheeze, Antibiotics
Brief summary
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
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.
Interventions
10 mg/kg for 3 consecutive days
OTHERPlacebo mixture
Placebo mixture containing no active substance
Sponsors
Copenhagen Studies on Asthma in Childhood
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 71 Months
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration in days of the asthma-like episode from the start of randomization. | 1-30 days | Number of days based on a diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect modification in relation to the child's respiratory microbiota profile. | Sample time, day 1 | Airway microbiota, pathogenic bacteria and vira as measured by 16S-rRNA and whole genome sequencing. |
| Effect modification in relation to the child's respiratory immunological profile. | Sample time, day 1 | Evaluation of immune mediator profiles (cytokine and chemokine levels) in the upper airway epithelial lining fluid. |
| The length of hospitalization (days) | 1-30 days | Determined by participants medical record. |
| Need for SABA during the asthma-like episode | 1-30 days | Number of days based on a diary. |
| Need for oral corticosteroids (OCS) during the asthma-like episode. | 1-30 days | Number of days based on a diary. |
| Change in symptom score. | From day 1 after randomization to completion of each randomized asthmatic episode aged 1-5 years. | 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). |
| Number of days away from daycare offers. | 1-30 days | Number of days based on a diary. |
| Health economic gain based on treatment costs and lost earnings. lost earnings for parent / guardian (s) | 1-30 days | The number of days home from daycare causing parent absenteeism due to illness based on this diary registration. |
| Gut microbiome profile | 1-30 days | Occurrence, diversity and abundance of gut microbiota using 16S rRNA sequencing and whole genome sequencing. |
| Resistance profiles | 1-30 days | Occurrence, diversity and abundance of antibiotic resistance genes as assessed by metagenome sequencing. |
| Adverse Event (AE) registration | 1-30 days | Number of events and type of event based on a diary. |
| Stratification of the above analyzes. | Sample time, day 1 | On the basis of the presence or absence of bacteria/microbiota in the respiratory tract, based on outcomes 3, 4 and 5. |
Countries
Denmark
Contacts
Primary ContactKlaus Bønnelykke, MD, PhD
Backup ContactUlrik Ralfkiaer, MSc, PhD
Outcome results
None listed