Clinical trial NCT05028153: Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms
Official title: Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms: A Double-blinded, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Childhood Asthma With Acute Exacerbation
Keywords: Asthma
Infections
Wheeze
Antibiotics
Lead sponsor: Copenhagen Studies on Asthma in Childhood
Sponsor class: OTHER
First posted: 2021-08-31
Enrollment: 320
Sex: ALL
Minimum age (years): 12
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Duration in days of the asthma-like episode from the start of randomization.
timeFrame: 1-30 days
Secondary outcomes:
measure: Change in symptom score.
timeFrame: From day 1 after randomization to completion of each randomized asthmatic episode aged 1-5 years.
measure: Effect modification in relation to the child's respiratory microbiota profile.
timeFrame: Sample time, day 1
measure: Effect modification in relation to the child's respiratory immunological profile.
timeFrame: Sample time, day 1
measure: The length of hospitalization (days)
timeFrame: 1-30 days
measure: Need for SABA during the asthma-like episode
timeFrame: 1-30 days
measure: Need for oral corticosteroids (OCS) during the asthma-like episode.
timeFrame: 1-30 days
measure: Stratification of the above analyzes.
timeFrame: Sample time, day 1
measure: Number of days away from daycare offers.
timeFrame: 1-30 days
measure: Health economic gain based on treatment costs and lost earnings. lost earnings for parent / guardian (s)
timeFrame: 1-30 days
measure: Gut microbiome profile
timeFrame: 1-30 days
measure: Resistance profiles
timeFrame: 1-30 days
measure: Adverse Event (AE) registration
timeFrame: 1-30 days
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: University Hospital of Copenhagen
Study officials:
affiliation: University Hospital of Copenhagen, DK-2820 Gentofte, Denmark
name: Jakob Stokholm, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kyvsgaard JN, Ralfkiaer U, Folsgaard N, Jensen TM, Hesselberg LM, Schoos AM, Bonnelykke K, Bisgaard H, Stokholm J, Chawes B. Azithromycin and high-dose vitamin D for treatment and prevention of asthma-like episodes in hospitalised preschool children: study protocol for a combined double-blind randomised controlled trial. BMJ Open. 2022 Apr 13;12(4):e054762. doi: 10.1136/bmjopen-2021-054762.