COPSACazt: Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms

Sponsor

Copenhagen Studies on Asthma in Childhood (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05028153

Collaborator

(none)

250

Enrollment

Arms

108

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Asthma With Acute Exacerbation	Drug: Azithromycin Oral Liquid Product Other: Placebo mixture	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2031

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Antibiotics

Azithromycin (10mg/kg) administered via oral suspension for 3 consecutive days

Drug: Azithromycin Oral Liquid Product

10 mg/kg for 3 consecutive days

Placebo Comparator: Placebo

Placebo with no active substance administered via oral suspension for 3 consecutive days

Other: Placebo mixture

Placebo mixture containing no active substance

Outcome Measures

Primary Outcome Measures

Duration in days of the asthma-like episode from the start of randomization. [1-21 days]
Number of days based on a diary.

Secondary Outcome Measures

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).
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) [1-21 days]
Determined by participants medical record.
Need for SABA during the asthma-like episode [1-21 days]
Number of days based on a diary.
Need for oral corticosteroids (OCS) during the asthma-like episode. [1-21 days]
Number of days 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.
Number of days away from daycare offers. [1-21 days]
Number of days based on a diary.
Health economic gain based on treatment costs and lost earnings. lost earnings for parent / guardian (s) [1-21 days]
The number of days home from daycare causing parent absenteeism due to illness based on this diary registration.
Gut microbiome profile [1-21 days]
Occurrence, diversity and abundance of gut microbiota using 16S rRNA sequencing and whole genome sequencing.
Resistance profiles [1-21 days]
Occurrence, diversity and abundance of antibiotic resistance genes as assessed by metagenome sequencing.
Adverse Event (AE) registration [1-21 days]
Number of events and type of event based on a diary.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 71 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).