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NCT Number: NCT07608328

Azithromycin to Modify Bronchiectasis Exacerbation Risk

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.

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Key information

Conditions

Non-cystic Fibrosis Bronchiectasis Bronchial Diseases Bronchiectasis Bronchiectasis Adult Bronchiectasis With Acute Exacerbation Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

About this study

The Azithromycin to Modify Bronchiectasis Exacerbation Risk (AMBER) trial is a prospective, randomized, double-blind, placebo-controlled, parallel-group superiority clinical trial conducted within the Assiut University bronchiectasis translational research platform.

The trial enrolls adults with clinically and radiologically confirmed non-cystic fibrosis bronchiectasis (NCFB). Participants will be randomized at the individual-patient level in a 1:1 allocation ratio to one of two treatment groups:

  • Standard care plus matching placebo once daily for 12 months.
  • Standard care plus azithromycin 250 mg orally once daily for 12 months.

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.

The primary objective is to determine whether azithromycin added to standard care reduces the occurrence of at least one bronchiectasis exacerbation during 12-month follow-up compared with matching placebo added to standard care.

The primary endpoint is occurrence of at least one bronchiectasis exacerbation during 12-month follow-up. A qualifying bronchiectasis exacerbation requires both clinically significant worsening of bronchiectasis-related respiratory symptoms and initiation or escalation of acute therapy. Acute therapy may include antibiotics, systemic corticosteroids where clinically indicated, intensified airway-clearance treatment, emergency assessment, or hospital admission.

Secondary clinical outcomes include total number of bronchiectasis exacerbations during follow-up, time to first bronchiectasis exacerbation, severe bronchiectasis exacerbation requiring hospitalization, bronchiectasis-related hospital admission, longitudinal change in forced expiratory volume in one second percent predicted (FEV1% predicted), resting room-air oxygen saturation measured by pulse oximetry (SpO2), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), Modified Medical Research Council dyspnea scale (mMRC), Bronchiectasis Health Questionnaire (BHQ) where systematically collected, and safety outcomes.

Safety outcomes include adverse events (AEs), serious adverse events (SAEs), gastrointestinal intolerance, cardiac symptoms or cardiac safety findings, QT prolongation or arrhythmia-related concern where assessed, treatment interruption, treatment discontinuation, clinically significant laboratory or symptom-based safety concerns, microbiological or resistance-related concerns where systematically collected, and death where applicable.

The trial uses a double-blind placebo-controlled design. Participants, treating clinicians, investigators involved in follow-up, outcome assessors, endpoint adjudicators where used, and investigators involved in outcome assessment will remain unaware of participant-level randomized treatment assignment until database lock unless emergency unblinding is required for participant safety. Study medication will be prepared in sequentially numbered containers according to the concealed randomization sequence.

The formal sample-size calculation is based on the primary binary endpoint. The calculation assumes a control-arm exacerbation occurrence of 60%, azithromycin-arm exacerbation occurrence of 40%, two-sided alpha level of 0.05, 90% statistical power, 1:1 allocation, and 10% allowance for attrition or incomplete endpoint ascertainment. The minimum attrition-adjusted requirement is 145 participants per arm. The planned AMBER randomized sample is at least 500 complete analyzable participants, with 250 participants per arm. If operationally feasible, randomized enrollment may extend to approximately 520 complete analyzable participants while preserving the 1:1 allocation ratio to improve precision for secondary and translational analyses.

The AMBER trial is scientifically linked to the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework and the Bronchiectasis Phenotype Identification Model (BPIM), which are separate locked methodological tools within the same translational platform. BASE and BPIM outputs will not be used for randomization stratification. If the relevant tool versions are locked and published before AMBER outcome analysis begins, BASE and BPIM may be applied for prespecified characterization, supportive adjustment, subgroup analysis, treatment-response interpretation, dynamic state occupancy analysis, and multistate transition analysis. No BASE or BPIM coefficient, threshold, class definition, score, model structure, or labeling rule will be recalculated, refitted, re-estimated, reweighted, recalibrated, or threshold-retuned using AMBER randomized treatment data.

Prespecified secondary translational analyses include longitudinal mixed-effects modeling, time-to-event analysis, exacerbation burden modeling, point-change analysis, mediation analysis, subgroup treatment-response heterogeneity analysis, dynamic BASE/BPIM state occupancy analysis, multistate and dynamic state transition analysis, correlation and regression analyses, joint longitudinal-survival modeling, sensitivity analyses, per-protocol supportive analysis, and safety analysis. These analyses are prespecified secondary translational analyses. They are not primary endpoints, are not interpreted as definitive primary treatment-effect tests, and will not replace the primary intention-to-treat (ITT) randomized comparison.

An independent Data Monitoring Committee (DMC) will monitor participant safety, serious adverse events, cardiac safety concerns, treatment discontinuation, recruitment progress, retention, and trial conduct. The DMC will operate independently from investigators responsible for participant recruitment, treatment delivery, endpoint assessment, and primary statistical analysis.

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.

In addition, the AMBER public preregistration is available through the Open Science Framework under DOI 10.17605/OSF.IO/RE54V.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • Suitable for baseline disease-signature assessment.
  • Able to undergo protocol-defined clinical, functional, radiological, oxygenation, inflammatory, symptom, and safety assessment.
  • Able to complete planned 12-month follow-up.
  • Eligible for randomization after baseline safety evaluation.
  • Written informed consent obtained from the participant or legal representative.

Exclusion criteria

  • 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.
  • Active malignancy or terminal non-respiratory illness expected to prevent planned follow-up.
  • Acute life-threatening illness preventing safe enrollment, baseline assessment, or randomization.
  • Recent major thoracic surgery or acute thoracic trauma interfering with baseline respiratory assessment.
  • Known hypersensitivity, contraindication, or serious intolerance to azithromycin or macrolide therapy.
  • Baseline cardiac findings judged by the investigator to make long-term azithromycin unsafe.
  • Requirement for long-term maintenance macrolide therapy at enrollment.
  • Current long-term maintenance macrolide use that cannot be safely discontinued before enrollment.
  • Inability to complete required baseline disease-signature assessment.
  • Inability or unwillingness to complete planned 12-month follow-up.
  • Refusal to participate.

Treatment and study plan

Standard Bronchiectasis Care

Other

Standard 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.

Other names: Routine bronchiectasis care

Azithromycin

Drug

Azithromycin 250 milligrams orally once daily for 12 months, added to standard bronchiectasis care.

Other names: Azithromycin 250 mg

Matching Placebo

Drug

Matching inert placebo tablet orally once daily for 12 months, added to standard bronchiectasis care. The placebo will not contain active azithromycin.

Other names: Matching placebo tablet

Primary outcomes

  1. Occurrence of at Least One Bronchiectasis Exacerbation During 12-Month Follow-Up

    Time frame: Baseline to 12 months 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.

Secondary outcomes

  1. Number of Bronchiectasis Exacerbations During 12-Month Follow-Up

    Time frame: Baseline to 12 months 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.

  2. Time to First Bronchiectasis Exacerbation

    Time frame: Baseline to 12 months follow-up.

    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.

  3. Occurrence of at Least One Severe Bronchiectasis Exacerbation Requiring Hospitalization

    Time frame: Baseline to 12 months follow-up.

    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.

  4. Occurrence of at Least One Bronchiectasis-Related Hospital Admission

    Time frame: Baseline to 12 months follow-up.

    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.

  5. Time to First Severe Bronchiectasis Exacerbation Requiring Hospitalization

    Time frame: Baseline to 12 months follow-up.

    Assessment of time from baseline to the first 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. Longer time to first severe hospitalized exacerbation indicates delayed severe clinical deterioration and favors azithromycin. Unit of measure: days.

  6. Time to First Bronchiectasis-Related Hospital Admission

    Time frame: Baseline to 12 months follow-up.

    Assessment of time from baseline to the first bronchiectasis-related hospital admission during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Longer time to first bronchiectasis-related hospital admission indicates delayed severe clinical deterioration and favors azithromycin. Unit of measure: days.

  7. Change in Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted) From Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in forced expiratory volume in one second percent predicted (FEV1% predicted) from baseline to Month 12. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater preservation or improvement in FEV1% predicted indicates better functional outcome and favors azithromycin. Unit of measure: percentage points.

  8. Change in Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2) From Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in resting room-air oxygen saturation measured by pulse oximetry (SpO2) from baseline to Month 12. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater preservation or improvement in SpO2 indicates better oxygenation outcome and favors azithromycin. Unit of measure: percentage points.

  9. Change in C-Reactive Protein (CRP) From Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in C-reactive protein (CRP) from baseline to Month 12. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in CRP indicates lower systemic inflammatory activity and favors azithromycin. Unit of measure: milligrams per liter.

  10. Change in Neutrophil-to-Lymphocyte Ratio (NLR) From Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Month 12. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in NLR indicates lower neutrophilic inflammatory activity and favors azithromycin. Unit of measure: ratio.

  11. Change in Modified Medical Research Council Dyspnea Scale (mMRC) Score from Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in Modified Medical Research Council dyspnea scale (mMRC) score from baseline to Month 12. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in mMRC score indicates lower dyspnea burden and favors azithromycin. Unit of measure: score on 0 to 4 scale.

  12. Change in Bronchiectasis Health Questionnaire (BHQ) Score From Baseline to Month 12

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in Bronchiectasis Health Questionnaire (BHQ) score from baseline to Month 12 where systematically collected. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Direction of better outcome will follow the standard BHQ scoring interpretation used in the trial. Unit of measure: BHQ score.

  13. Occurrence of Any Adverse Event (AE)

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience at least one adverse event (AE) during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better tolerability and safety profile. Unit of measure: percentage of participants.

  14. Occurrence of Any Serious Adverse Event (SAE)

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience at least one serious adverse event (SAE) during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better serious safety profile. Unit of measure: percentage of participants.

  15. Occurrence of Gastrointestinal Intolerance

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience gastrointestinal intolerance during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better gastrointestinal tolerability. Unit of measure: percentage of participants.

  16. Occurrence of Cardiac Safety Concern

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience a cardiac safety concern during follow-up. This composite endpoint includes cardiac symptoms, clinically relevant cardiac findings, QT prolongation, or arrhythmia-related concern where assessed. Lower occurrence indicates better cardiac safety profile. Unit of measure: percentage of participants.

  17. Occurrence of Ototoxicity-Related Safety Concern

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience an ototoxicity-related safety concern during follow-up, including hearing loss, tinnitus, or related clinically documented symptoms where assessed. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better ototoxicity safety profile. Unit of measure: percentage of participants.

  18. Occurrence of Hepatotoxicity-Related Safety Concern

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience a hepatotoxicity-related safety concern during follow-up, including clinically significant liver enzyme elevation or liver-related adverse clinical concern where assessed. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better hepatotoxicity safety profile. Unit of measure: percentage of participants.

  19. Treatment Interruption

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who experience temporary interruption of assigned study medication during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better treatment continuity and tolerability. Unit of measure: percentage of participants.

  20. Treatment Discontinuation Proportion

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who permanently discontinue assigned study medication during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower occurrence indicates better treatment persistence and tolerability. Unit of measure: percentage of participants.

  21. Time to Treatment Discontinuation

    Time frame: Baseline to 12 months follow-up.

    Assessment of time from baseline to permanent discontinuation of assigned study medication during follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Longer time to treatment discontinuation indicates better treatment persistence and tolerability. Unit of measure: days.

  22. All-Cause Mortality During 12-Month Follow-Up

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who die from any cause during 12-month follow-up. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower all-cause mortality indicates better survival outcome. Unit of measure: percentage of participants.

Other outcomes

  1. Proportion of Participants with Zero Bronchiectasis Exacerbations

    Time frame: Baseline to 12 months follow-up.

    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.

  2. Proportion of Participants with Two or More Bronchiectasis Exacerbations

    Time frame: Baseline to 12 months follow-up.

    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.

  3. Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months 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.

  4. Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months 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.

  5. C-Reactive Protein (CRP) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months follow-up.

    Assessment of repeated C-reactive protein (CRP) measurements across planned follow-up visits. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in CRP trajectory indicates lower systemic inflammatory activity and favors azithromycin. Unit of measure: milligrams per liter.

  6. Neutrophil-to-Lymphocyte Ratio (NLR) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months follow-up.

    Assessment of repeated neutrophil-to-lymphocyte ratio (NLR) measurements across planned follow-up visits. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in NLR trajectory indicates lower neutrophilic inflammatory activity and favors azithromycin. Unit of measure: ratio.

  7. Modified Medical Research Council Dyspnea Scale (mMRC) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months follow-up.

    Assessment of repeated Modified Medical Research Council dyspnea scale (mMRC) scores across planned follow-up visits. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater reduction in mMRC trajectory indicates lower dyspnea burden and favors azithromycin. Unit of measure: score on 0 to 4 scale.

  8. Bronchiectasis Health Questionnaire (BHQ) Trajectory Over Follow-Up

    Time frame: Baseline to 12 months follow-up.

    Assessment of repeated Bronchiectasis Health Questionnaire (BHQ) scores across planned follow-up visits where systematically collected. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Direction of better outcome will follow the standard BHQ scoring interpretation used in the trial. Unit of measure: BHQ score.

  9. Mediation of Treatment Effect by Change in C-Reactive Protein (CRP)

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether change in C-reactive protein (CRP) mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related change in CRP contributes to the treatment effect. Unit of measure: percentage.

  10. Mediation of Treatment Effect by Change in Neutrophil-to-Lymphocyte Ratio (NLR)

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether change in neutrophil-to-lymphocyte ratio (NLR) mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related change in NLR contributes to the treatment effect. Unit of measure: percentage.

  11. Mediation of Treatment Effect by Change in Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted)

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether change in forced expiratory volume in one second percent predicted (FEV1% predicted) mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related change in FEV1% predicted contributes to the treatment effect. Unit of measure: percentage.

  12. Mediation of Treatment Effect by Change in Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2)

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether change in resting room-air oxygen saturation measured by pulse oximetry (SpO2) mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related change in SpO2 contributes to the treatment effect. Unit of measure: percentage.

  13. Mediation of Treatment Effect by Change in Modified Medical Research Council Dyspnea Scale (mMRC)

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether change in Modified Medical Research Council dyspnea scale (mMRC) mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related change in mMRC contributes to the treatment effect. Unit of measure: percentage.

  14. Mediation of Treatment Effect by Microbiological Change

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether microbiological change mediates the effect of randomized treatment assignment on bronchiectasis exacerbation outcomes where systematically collected. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A higher proportion mediated indicates greater evidence that treatment-related microbiological change contributes to the treatment effect. Unit of measure: percentage.

  15. Treatment-Response Heterogeneity by Age Group

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by prespecified age group. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by age group. Unit of measure: interaction effect estimate.

  16. Treatment-Response Heterogeneity by Sex

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by sex. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by sex. Unit of measure: interaction effect estimate.

  17. Treatment-Response Heterogeneity by Baseline Frequent Exacerbator Status

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by baseline frequent exacerbator status. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by baseline frequent exacerbator status. Unit of measure: interaction effect estimate.

  18. Treatment-Response Heterogeneity by Baseline Inflammatory Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by baseline inflammatory burden. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by baseline inflammatory burden. Unit of measure: interaction effect estimate.

  19. Treatment-Response Heterogeneity by Baseline Functional Impairment

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by baseline functional impairment. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by baseline functional impairment. Unit of measure: interaction effect estimate.

  20. Treatment-Response Heterogeneity by Baseline Oxygenation Impairment

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by baseline oxygenation impairment. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by baseline oxygenation impairment. Unit of measure: interaction effect estimate.

  21. Treatment-Response Heterogeneity by Chronic Airway Colonization Status

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by chronic airway colonization status. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by chronic airway colonization status. Unit of measure: interaction effect estimate.

  22. Treatment-Response Heterogeneity by Pseudomonas aeruginosa Status

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by Pseudomonas aeruginosa status. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by Pseudomonas aeruginosa status. Unit of measure: interaction effect estimate.

  23. Treatment-Response Heterogeneity by Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) State

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) state, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by BASE-S state. Unit of measure: interaction effect estimate.

  24. Treatment-Response Heterogeneity by Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk State

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk state, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by BASE-P risk state. Unit of measure: interaction effect estimate.

  25. Treatment-Response Heterogeneity by Bronchiectasis Phenotype Identification Model (BPIM) Predicted Phenotype State

    Time frame: Baseline to 12 months follow-up.

    Assessment of whether treatment effect on bronchiectasis exacerbation outcomes differs by Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype state, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A larger interaction effect indicates stronger evidence that treatment response differs by BPIM predicted phenotype state. Unit of measure: interaction effect estimate.

  26. Visit-Level Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) State Occupancy

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants assigned to each Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) state at each planned visit, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A shift toward more favorable BASE-S states indicates better disease-state profile. Unit of measure: percentage of participants.

  27. Visit-Level Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk State Occupancy

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants assigned to each Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk state at each planned visit, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A shift toward lower-risk BASE-P states indicates better prognostic state profile. Unit of measure: percentage of participants.

  28. Visit-Level Bronchiectasis Phenotype Identification Model (BPIM) Predicted Phenotype State Occupancy

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants assigned to each Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype state at each planned visit, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. A shift toward more favorable BPIM phenotype states indicates better disease-state profile. Unit of measure: percentage of participants.

  29. Baseline-to-Month-12 Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) State Transition

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) state from baseline to Month 12, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater movement toward favorable BASE-S states indicates better disease-state transition. Unit of measure: percentage of participants in each transition category.

  30. Baseline-to-Month-12 Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk State Transition

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk state from baseline to Month 12, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater movement toward lower-risk BASE-P states indicates better prognostic transition. Unit of measure: percentage of participants in each transition category.

  31. Baseline-to-Month-12 Bronchiectasis Phenotype Identification Model (BPIM) Phenotype State Transition

    Time frame: Baseline to 12 months follow-up.

    Assessment of change in Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype state from baseline to Month 12, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Greater movement toward favorable BPIM phenotype states indicates better disease-state transition. Unit of measure: percentage of participants in each transition category.

  32. Number of Visits Spent in Favorable Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in favorable Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Higher values indicate more sustained favorable BASE-S state occupancy and favor azithromycin. Unit of measure: number of visits.

  33. Number of Visits Spent in Unfavorable Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in unfavorable Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower values indicate less unfavorable BASE-S state occupancy and favor azithromycin. Unit of measure: number of visits.

  34. Number of Visits Spent in Favorable Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in favorable Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Higher values indicate more sustained favorable BASE-P risk-state occupancy and favor azithromycin. Unit of measure: number of visits.

  35. Number of Visits Spent in Unfavorable Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in unfavorable Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower values indicate less unfavorable BASE-P risk-state occupancy and favor azithromycin. Unit of measure: number of visits.

  36. Number of Visits Spent in Favorable Bronchiectasis Phenotype Identification Model (BPIM) Phenotype States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in favorable Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Higher values indicate more sustained favorable BPIM phenotype-state occupancy and favor azithromycin. Unit of measure: number of visits.

  37. Number of Visits Spent in Unfavorable Bronchiectasis Phenotype Identification Model (BPIM) Phenotype States

    Time frame: Baseline to 12 months follow-up.

    Assessment of the number of planned visits each participant spends in unfavorable Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype states, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Lower values indicate less unfavorable BPIM phenotype-state occupancy and favor azithromycin. Unit of measure: number of visits.

  38. Multistate Transition Pattern of Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) States

    Time frame: Baseline to 12 months follow-up.

    Assessment of transition patterns between Bronchiectasis Assessment of Severity and Exacerbations Severity Model (BASE-S) states over follow-up, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Transition toward more favorable BASE-S states indicates better disease-state movement. Unit of measure: transition probability.

  39. Multistate Transition Pattern of Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) Risk States

    Time frame: Baseline to 12 months follow-up.

    Assessment of transition patterns between Bronchiectasis Assessment of Severity and Exacerbations Prognostic Model (BASE-P) risk states over follow-up, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Transition toward lower-risk BASE-P states indicates better prognostic movement. Unit of measure: transition probability.

  40. Multistate Transition Pattern of Bronchiectasis Phenotype Identification Model (BPIM) Phenotype States

    Time frame: Baseline to 12 months follow-up.

    Assessment of transition patterns between Bronchiectasis Phenotype Identification Model (BPIM) predicted phenotype states over follow-up, if the tool is locked before analysis. Randomized treatment assignment compares standard bronchiectasis care plus azithromycin with standard bronchiectasis care plus matching placebo. Transition toward more favorable BPIM phenotype states indicates better disease-state movement. Unit of measure: transition probability.

  41. Joint Longitudinal-Survival Association Between Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted) Trajectory and Time to First Bronchiectasis Exacerbation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the model-derived association parameter from a prespecified joint longitudinal-survival model combining repeated forced expiratory volume in one second percent predicted (FEV1% predicted) measurements with time to first qualifying bronchiectasis exacerbation during 12-month follow-up. The longitudinal marker and the time-to-event endpoint will be combined within a single joint model to generate one reported association estimate. A stronger association indicates greater linkage between functional trajectory and exacerbation timing. Unit of measure: hazard ratio.

  42. Joint Longitudinal-Survival Association Between Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2) Trajectory and Time to First Bronchiectasis Exacerbation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the model-derived association parameter from a prespecified joint longitudinal-survival model combining repeated resting room-air oxygen saturation measured by pulse oximetry (SpO2) measurements with time to first qualifying bronchiectasis exacerbation during 12-month follow-up. The longitudinal marker and the time-to-event endpoint will be combined within a single joint model to generate one reported association estimate. A stronger association indicates greater linkage between oxygenation trajectory and exacerbation timing. Unit of measure: hazard ratio.

  43. Joint Longitudinal-Survival Association Between C-Reactive Protein (CRP) Trajectory and Time to First Bronchiectasis Exacerbation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the model-derived association parameter from a prespecified joint longitudinal-survival model combining repeated C-reactive protein (CRP) measurements with time to first qualifying bronchiectasis exacerbation during 12-month follow-up. The longitudinal marker and the time-to-event endpoint will be combined within a single joint model to generate one reported association estimate. A stronger association indicates greater linkage between systemic inflammatory trajectory and exacerbation timing. Unit of measure: hazard ratio.

  44. Joint Longitudinal-Survival Association Between Neutrophil-to-Lymphocyte Ratio (NLR) Trajectory and Time to First Bronchiectasis Exacerbation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the model-derived association parameter from a prespecified joint longitudinal-survival model combining repeated neutrophil-to-lymphocyte ratio (NLR) measurements with time to first qualifying bronchiectasis exacerbation during 12-month follow-up. The longitudinal marker and the time-to-event endpoint will be combined within a single joint model to generate one reported association estimate. A stronger association indicates greater linkage between neutrophilic inflammatory trajectory and exacerbation timing. Unit of measure: hazard ratio.

  45. Correlation Between C-Reactive Protein (CRP) Change and Exacerbation Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of the association between change in C-reactive protein (CRP) from baseline to Month 12 and total bronchiectasis exacerbation burden during 12-month follow-up. The reported value will be a single correlation coefficient describing the relationship between changes in CRP and the total qualifying bronchiectasis exacerbation count. A stronger correlation indicates a greater association between systemic inflammatory changes and exacerbation burden. Unit of measure: correlation coefficient.

  46. Correlation Between Neutrophil-to-Lymphocyte Ratio (NLR) Change and Exacerbation Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of the association between change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Month 12 and total bronchiectasis exacerbation burden during 12-month follow-up. The reported value will be a single correlation coefficient describing the relationship between the change in NLR and the total qualifying bronchiectasis exacerbation count. A stronger correlation indicates a greater association between neutrophilic inflammatory change and exacerbation burden. Unit of measure: correlation coefficient.

  47. Correlation Between Functional Change and Exacerbation Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of the association between change in forced expiratory volume in one second percent predicted (FEV1% predicted) and total bronchiectasis exacerbation burden during follow-up. Stronger correlation indicates greater linkage between functional change and exacerbation burden. Unit of measure: correlation coefficient.

  48. Correlation Between Oxygenation Change and Exacerbation Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of the association between change in resting room-air oxygen saturation measured by pulse oximetry (SpO2) and total bronchiectasis exacerbation burden during follow-up. Stronger correlation indicates greater linkage between oxygenation change and exacerbation burden. Unit of measure: correlation coefficient.

  49. Correlation Between Modified Medical Research Council Dyspnea Scale (mMRC) Change and Exacerbation Burden

    Time frame: Baseline to 12 months follow-up.

    Assessment of the association between change in Modified Medical Research Council dyspnea scale (mMRC) score and total bronchiectasis exacerbation burden during follow-up. Stronger correlation indicates greater linkage between symptom change and exacerbation burden. Unit of measure: correlation coefficient.

  50. Antimicrobial-Resistance Safety Concern

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants with a new clinically relevant antimicrobial-resistance concern during follow-up where systematically collected. Lower occurrence indicates better antimicrobial-resistance safety profile. Unit of measure: percentage of participants.

  51. New Clinically Relevant Microbiological Isolation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants with new clinically relevant microbiological isolation during follow-up where systematically collected. Lower occurrence indicates better microbiological safety profile. Unit of measure: percentage of participants.

  52. Clinically Required Long-Term Maintenance Macrolide Crossover

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants who require long-term maintenance macrolide therapy outside assigned trial treatment during follow-up. This endpoint captures clinically required non-protocol maintenance macrolide crossover. Lower occurrence indicates less need for external maintenance macrolide therapy. Unit of measure: percentage of participants.

  53. Protocol-Defined Major Deviation

    Time frame: Baseline to 12 months follow-up.

    Assessment of the proportion of participants with a protocol-defined major deviation during follow-up. Major deviations may include serious eligibility, treatment exposure, prohibited therapy, endpoint ascertainment, or follow-up deviations according to the locked protocol. Lower occurrence indicates better protocol adherence and trial conduct. Unit of measure: percentage of participants.

Study contacts

Contact information is provided by the study sponsor or research team.

Ahmad M Shaddad, MD

CONTACT

[email protected]

+201111171930

Sponsors and collaborators

Lead sponsor

Assiut University

Other

Registry information

Official study title

AMBER: Azithromycin to Modify Bronchiectasis Exacerbation Risk - A Double-Blind Placebo-Controlled Randomized Trial in Adults With Non-Cystic Fibrosis Bronchiectasis

Acronym: AMBER

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 27, 2026
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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