Azithromycin Treatment of Hospitalized Children With Asthmatic Symptoms (COPSACazt)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Childhood Asthma With Acute Exacerbation
• Intervention / Treatment: Drug: Azithromycin Oral Liquid Product; Other: Placebo mixture

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 Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Klaus Bønnelykke, MD, PhD; Phone Number: +4538677360; Email: kb@copsac.com
• Study Contact Backup: Name: Ulrik Ralfkiaer, MSc, PhD; Phone Number: +4538674164; Email: administration@dbac.dk

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Recruiting
    • University Hospital of Copenhagen
    • Contact: Klaus Bønnelykke, MD, PhD; Phone Number: +45 3867 7360; Email: kb@copsac.com
    • Contact: Ulrik Ralfkiaer, MSc, PhD; Phone Number: +45 3867 4164; Email: administration@dbac.dk
    • Contact: Jakob Stokholm, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Copenhagen Studies on Asthma in Childhood
• Investigators: Principal Investigator: Jakob Stokholm, MD, PhD, University Hospital of Copenhagen, DK-2820 Gentofte, Denmark

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): November 13, 2032

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 9, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Asthma; Antibiotics; Infections; Wheeze
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin
• Other Study ID Numbers: H-20065249

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No