Enhancing Lung Health in Kids With Structural Lung Damage and Malformations: Azithromycin (AZI) for Airway Infection Prevention (TRALULALA-AZI)

Enhancing Lung Health in Kids With Structural Lung Damage and Malformations: a Randomized Controlled Trial on Azithromycin (AZI) for Airway Infection Prevention

Children with lung and airway malformations or early structural lung damage face significant challenges, often leading to recurrent respiratory infections, hospitalizations, and decreased quality of life. Despite various interventions, effective strategies are urgently needed.

The link between these conditions and persistent bacterial bronchitis remains unclear, possibly due to compromised airways and reduced mucociliary clearance. Although antibiotics can alleviate symptoms, relapse is common.

Experts often prescribe prophylactic azithromycin, despite limited evidence of its benefits. Azithromycin shows promise due to its anti-inflammatory and immunomodulatory effects but lacks thorough evaluation in this population.

To address this gap, we propose a double-blind, randomized controlled trial to assess azithromycin's effectiveness and safety in preventing respiratory infections in children with these conditions. This research aims to inform clinical practice and improve the health of affected children and their families.

Study Overview

• Status: Not yet recruiting
• Conditions: Bronchiectasis; Bronchopulmonary Dysplasia (BPD); Tracheomalacia; Cystic Lung Disease; Vascular Ring; Chronic Atelectasis
• Intervention / Treatment: Other: Placebo; Drug: Azithromycin 40 MG/ML

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. CT and bronchoscopy verified and structural lung damage or congenital lung and airway malformations
2. Outpatient affiliation with one of the three highly specialized pediatric pulmonology centers.
3. At risk of or already documented respiratory infections requiring antibiotics.
4. Age between 0-72 months at inclusion.

Exclusion Criteria:

1. Asthmatic challenges: Patients without any of the conditions mentioned in table 1 repeatedly experiencing asthmatic problems are not eligible for this study.
2. Cystic fibrosis (CF) or primary ciliary dyskinesia (PCD): Patients with a CF or PCD diagnosis will be excluded.
3. Impaired liver function: Children with an alanine transaminase (ALAT) twice or more the upper limits of normal will be excluded.
4. Impaired kidney function: Children with a serum creatinine higher than the upper limit of normal for age will be excluded.
5. Neurological or psychiatric disorders
6. Prolonged QT interval: Patients with either congenital or acquired prolonged QT interval will be excluded.
7. Heart disease: Patients with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure are not eligible for this study.
8. Allergy to macrolide antibiotics: documented allergy to macrolide antibiotics (extremely rare) will result in exclusion from the study.

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: Azithromycin Oral Suspension 40 mg/ml	Drug: Azithromycin 40 MG/ML; Maintenance Antibiotic treatment
Placebo Comparator: Placebo Oral suspension	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of exacerbations	Number of exacerbations where systemic antibiotics is needed within the study period	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of exacerbations	Duration of exacerbations, hospitalizations and durations of hospitalizations	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function measures	Impulse oscillometry (IOS) measurement pre- and post drug administrations	1 year
Quality of Life	Questionaire on a Likert scale 0-5. Using PedsQL(TM).	1 year

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Lung Injury; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Vascular Malformations; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Aortic Diseases; Cartilage Diseases; Tracheal Diseases; Aortic Arch Syndromes; Tracheobronchomalacia; Bronchiectasis; Lung Diseases; Pulmonary Atelectasis; Bronchopulmonary Dysplasia; Tracheomalacia; Vascular Ring; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: p-2024-15966

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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