The Azithromycin to Modify Bronchiectasis Exacerbation Risk (AMBER) trial is a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial in adults with clinically and radiologically confirmed non-cystic fibrosis bronchiectasis (NCFB).
The trial evaluates whether azithromycin 250 mg orally once daily for 12 months, added to standard bronchiectasis care, reduces the occurrence of at least one bronchiectasis exacerbation during 12-month follow-up compared with matching placebo added to standard bronchiectasis care.
Participants will be randomized in a 1:1 allocation ratio to standard care plus matching placebo or standard care plus azithromycin. The primary analysis will follow the intention-to-treat (ITT) principle.
The AMBER trial is embedded within the Assiut University bronchiectasis translational research platform and is linked to the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework and the Bronchiectasis Phenotype Identification Model (BPIM). BASE and BPIM are not used for randomization stratification and will not modify the primary randomized comparison.
The locked Version 1.0 methodological disclosure document, protocol, and statistical analysis plan (SAP), primary sample-size source code, and endpoint-level sample-size support matrix are archived in Zenodo: https://doi.org/10.5281/zenodo.20178963.
The AMBER public preregistration is also available through the Open Science Framework (OSF) under Digital Object Identifier (DOI) 10.17605/OSF.IO/RE54V.
Adult patients aged 18 years or older.
Clinically and radiologically confirmed non-cystic fibrosis bronchiectasis (NCFB).
Diagnosis supported by clinical assessment and high-resolution computed tomography (HRCT).
Patients attending outpatient clinics, inpatient wards, respiratory follow-up services, or routine bronchiectasis care pathways at Assiut University Hospitals during the enrollment period.
Cystic fibrosis-related bronchiectasis.
Traction bronchiectasis due to advanced fibrotic interstitial lung disease as the dominant respiratory diagnosis.
Active pulmonary tuberculosis at enrollment.
Active nontuberculous mycobacterial pulmonary disease requiring specific treatment at enrollment.
Parallel
Standard Bronchiectasis Care
Other interventionStandard bronchiectasis care provided in both randomized groups according to institutional practice and treating physician judgment. Standard bronchiectasis care may include mucolytics, bronchodilators, chest physiotherapy, patient education, airway-clearance support, and treatment of acute exacerbations with antibiotics with or without systemic corticosteroids according to clinical indication. Standard bronchiectasis care is provided as shared background care in both arms and is not the randomized treatment contrast. Clinically required rescue or emergency care remains permitted according to treating physician judgment.
Azithromycin
DrugAzithromycin 250 milligrams orally once daily for 12 months, added to standard bronchiectasis care.
Matching Placebo
DrugMatching inert placebo tablet orally once daily for 12 months, added to standard bronchiectasis care. The placebo will not contain active azithromycin.
Occurrence of at Least One Bronchiectasis Exacerbation During 12-Month Follow-Up
Assessment of the proportion of participants who experience at least one qualifying bronchiectasis exacerbation during 12-month follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A qualifying exacerbation requires both clinically significant worsening of bronchiectasis-related respiratory symptoms and initiation or escalation of acute therapy. Lower occurrence indicates better clinical outcome and favors azithromycin. Unit of measure: percentage of participants.
Number of Bronchiectasis Exacerbations During 12-Month Follow-Up
Assessment of the total number of qualifying bronchiectasis exacerbations experienced by each participant during 12-month follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A lower exacerbation count indicates lower exacerbation burden and favors azithromycin. Unit of measure: number of events.
Time to First Bronchiectasis Exacerbation
Assessment of time from baseline to the first qualifying bronchiectasis exacerbation during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Longer time to first exacerbation indicates delayed clinical deterioration and favors azithromycin. Unit of measure: days.
Occurrence of at Least One Severe Bronchiectasis Exacerbation Requiring Hospitalization
Assessment of the proportion of participants who experience at least one qualifying bronchiectasis exacerbation requiring hospital admission during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates fewer severe exacerbation events and favors azithromycin. Unit of measure: percentage of participants.
Occurrence of at Least One Bronchiectasis-Related Hospital Admission
Assessment of the proportion of participants who experience at least one bronchiectasis-related hospital admission during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates lower hospital-use burden and favors azithromycin. Unit of measure: percentage of participants.
Proportion of Participants with Zero Bronchiectasis Exacerbations
Assessment of the proportion of participants who experience no qualifying bronchiectasis exacerbation during 12-month follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Higher zero-exacerbation occurrence indicates better exacerbation prevention and favors azithromycin. Unit of measure: percentage of participants.
Proportion of Participants with Two or More Bronchiectasis Exacerbations
Assessment of the proportion of participants who experience two or more qualifying bronchiectasis exacerbations during 12-month follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates lower recurrent exacerbation burden and favors azithromycin. Unit of measure: percentage of participants.
Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted) Trajectory Over Follow-Up
Assessment of repeated forced expiratory volume in one second percent predicted (FEV1% predicted) measurements across planned follow-up visits. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater preservation or improvement in FEV1% predicted trajectory indicates better functional outcome and favors azithromycin. Unit of measure: percentage points.
Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2) Trajectory Over Follow-Up
Assessment of repeated resting room-air oxygen saturation measured by pulse oximetry (SpO2) across planned follow-up visits. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater preservation or improvement in SpO2 trajectory indicates better oxygenation outcome and favors azithromycin. Unit of measure: percentage points.
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