Non-cystic Fibrosis BronchiectasisPhase 4AMBERNCT07608328
Azithromycin to Modify Bronchiectasis Exacerbation Risk
A Phase 4 study testing Standard Bronchiectasis Care and Azithromycin in people with Non-cystic Fibrosis Bronchiectasis and Bronchiectasis Adult, run by Assiut University at 1 site in Egypt.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-cystic Fibrosis Bronchiectasis, Bronchiectasis Adult, Bronchiectasis
- What is being tested?
- Standard Bronchiectasis Care and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 1 siteEgypt
- Study dates
- 29 Jun 2026to 30 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site, 1 recruiting
- Recruiting
Assiut university-Faculty of Medicine
Asyut, 71515
Ahmad M Shaddad, MD, +201111171930, shaddad_ahmad@aun.edu.eg
About this study
Official title: AMBER: Azithromycin to Modify Bronchiectasis Exacerbation Risk - A Double-Blind Placebo-Controlled Randomized Trial in Adults With Non-Cystic Fibrosis Bronchiectasis
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Non-cystic Fibrosis Bronchiectasis, Bronchiectasis Adult, Bronchiectasis, Bronchiectasis With Acute Exacerbation
- Being tested
- Standard Bronchiectasis Care, Azithromycin, Matching Placebo
- Keywords
- Non-cystic fibrosis bronchiectasis (NCFB), Bronchiectasis, Bronchiectasis exacerbation, Exacerbation risk, azithromycin, macrolide therapy, double-blind placebo-controlled trial, randomized controlled trial (RCT), 12-month follow-up, Assiut University
- Medical subject headings
- Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Bronchiectasis CareOther
Also called Routine bronchiectasis care
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.
AzithromycinDrug
Also called Azithromycin 250 mg
Azithromycin 250 milligrams orally once daily for 12 months, added to standard bronchiectasis care.
Matching PlaceboDrug
Also called Matching placebo tablet
Matching inert placebo tablet orally once daily for 12 months, added to standard bronchiectasis care. The placebo will not contain active azithromycin.
| Study group | Role | What they receive |
|---|---|---|
| Placebo Control Arm | Placebo comparator | Participants assigned to this arm will receive standard bronchiectasis care plus matching placebo once daily for 12 months. Standard 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 matching placebo will not contain active azithromycin. Receives: Other: Standard Bronchiectasis Care; Drug: Matching Placebo |
| Experimental Azithromycin Arm | Experimental | Participants assigned to this arm will receive standard bronchiectasis care plus azithromycin 250 milligrams orally once daily for 12 months. Standard 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. Receives: Other: Standard Bronchiectasis Care; Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 months follow-up.
Secondary outcomes (22)
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.
Measured: Baseline to 12 months follow-up.
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.
Measured: Baseline to 12 months follow-up.
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.
Measured: Baseline to 12 months follow-up.
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.
Measured: Baseline to 12 months follow-up.
Time to First Severe Bronchiectasis Exacerbation Requiring Hospitalization
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.
Measured: Baseline to 12 months follow-up.
Time to First Bronchiectasis-Related Hospital Admission
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.
Measured: Baseline to 12 months follow-up.
Change in Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted) From Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Change in Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO2) From Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Change in C-Reactive Protein (CRP) From Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Change in Neutrophil-to-Lymphocyte Ratio (NLR) From Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Change in Modified Medical Research Council Dyspnea Scale (mMRC) Score from Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Change in Bronchiectasis Health Questionnaire (BHQ) Score From Baseline to Month 12
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Any Adverse Event (AE)
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Any Serious Adverse Event (SAE)
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Gastrointestinal Intolerance
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Cardiac Safety Concern
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Ototoxicity-Related Safety Concern
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.
Measured: Baseline to 12 months follow-up.
Occurrence of Hepatotoxicity-Related Safety Concern
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.
Measured: Baseline to 12 months follow-up.
Treatment Interruption
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.
Measured: Baseline to 12 months follow-up.
Treatment Discontinuation Proportion
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.
Measured: Baseline to 12 months follow-up.
Time to Treatment Discontinuation
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.
Measured: Baseline to 12 months follow-up.
All-Cause Mortality During 12-Month 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.
Measured: Baseline to 12 months follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study start29 Jun 2026
- Primary completion21 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-cystic Fibrosis BronchiectasisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 1:1 allocation ratio to one of two parallel treatment groups: standard care plus matching placebo once daily for 12 months or standard care plus azithromycin 250 mg orally once daily for 12 months.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmad Shaddad, Assiut University
- Investigators
- Ahmad M. Shaddad, MD, Principal investigator, Assiut UniversityAliae M. Hussien, MD, Principal investigator, Assiut UniversityMaiada K. Hashem, MD, Principal investigator, Assiut UniversityAlaa S. Ali, Principal investigator, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07608328
- Sponsor's protocol ID
- 2026-5-51
- Other IDs
- 10.5281/zenodo.20178963, 10.17605/OSF.IO/RE54V
- Acronym
- AMBER
- Status last verified
- Sep 2026
- First submitted
- 15 May 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the reported AMBER trial results may be shared only upon reasonable scientific request and after approval by the principal investigator, Faculty of Medicine, Assiut University, and the relevant ethics committee or institutional authority where applicable. Shared data will exclude directly identifiable participant information and will be limited to variables necessary for the approved scientific purpose. The AMBER protocol, statistical analysis plan (SAP), informed consent form (ICF), and related methodological materials remain governed by the institutional and investigator approval process. Protected analytical code, model implementation materials, Bronchiectasis Assessment of Severity and Exacerbations (BASE) materials, and Bronchiectasis Phenotype Identification Model (BPIM) materials are not automatically shared with IPD and require separate written authorization.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AMBER: Azithromycin to Modify Bronchiectasis Exacerbation Risk - A Double-Blind Placebo-Controlled Randomized Trial in Adults With Non-Cystic Fibrosis Bronchiectasis
- ClinicalTrials.gov ID
- NCT07608328
- Acronym / sponsor ID
- AMBER / 2026-5-51
- Conditions
- Non-cystic Fibrosis Bronchiectasis, Bronchiectasis Adult, Bronchiectasis, Bronchiectasis With Acute Exacerbation
- Keywords
- Non-cystic fibrosis bronchiectasis (NCFB), Bronchiectasis, Bronchiectasis exacerbation, Exacerbation risk, azithromycin, macrolide therapy, double-blind placebo-controlled trial, randomized controlled trial (RCT)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 29 Jun 2026 (actual)
- Primary completion
- 21 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 27 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized in a 1:1 allocation ratio to one of two parallel treatment groups: standard care plus matching placebo once daily for 12 months or standard care plus azithromycin 250 mg orally once daily for 12 months.
| Arm | Type | Receives |
|---|---|---|
| Placebo Control Arm | Placebo comparator | Other: Standard Bronchiectasis Care, Drug: Matching PlaceboParticipants assigned to this arm will receive standard bronchiectasis care plus matching placebo once daily for 12 months. Standard 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 matching placebo will not contain active azithromycin. |
| Experimental Azithromycin Arm | Experimental | Other: Standard Bronchiectasis Care, Drug: AzithromycinParticipants assigned to this arm will receive standard bronchiectasis care plus azithromycin 250 milligrams orally once daily for 12 months. Standard 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Bronchiectasis CareAlso: Routine bronchiectasis careStandard 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 | Experimental Azithromycin Arm, Placebo Control Arm |
| AzithromycinAlso: Azithromycin 250 mgAzithromycin 250 milligrams orally once daily for 12 months, added to standard bronchiectasis care. | Drug | Experimental Azithromycin Arm |
| Matching PlaceboAlso: Matching placebo tabletMatching inert placebo tablet orally once daily for 12 months, added to standard bronchiectasis care. The placebo will not contain active azithromycin. | Drug | Placebo Control Arm |
Primary outcome
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.
22 secondary outcomes
Number of Bronchiectasis Exacerbations During 12-Month Follow-Up
Time frame: Baseline to 12 months follow-up.
Time to First Bronchiectasis Exacerbation
Time frame: Baseline to 12 months follow-up.
Occurrence of at Least One Severe Bronchiectasis Exacerbation Requiring Hospitalization
Time frame: Baseline to 12 months follow-up.
Occurrence of at Least One Bronchiectasis-Related Hospital Admission
Time frame: Baseline to 12 months follow-up.
Time to First Severe Bronchiectasis Exacerbation Requiring Hospitalization
Time frame: Baseline to 12 months follow-up.
Time to First Bronchiectasis-Related Hospital Admission
Time frame: Baseline to 12 months follow-up.
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.
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.
Change in C-Reactive Protein (CRP) From Baseline to Month 12
Time frame: Baseline to 12 months follow-up.
Change in Neutrophil-to-Lymphocyte Ratio (NLR) From Baseline to Month 12
Time frame: Baseline to 12 months follow-up.
Change in Modified Medical Research Council Dyspnea Scale (mMRC) Score from Baseline to Month 12
Time frame: Baseline to 12 months follow-up.
Change in Bronchiectasis Health Questionnaire (BHQ) Score From Baseline to Month 12
Time frame: Baseline to 12 months follow-up.
Occurrence of Any Adverse Event (AE)
Time frame: Baseline to 12 months follow-up.
Occurrence of Any Serious Adverse Event (SAE)
Time frame: Baseline to 12 months follow-up.
Occurrence of Gastrointestinal Intolerance
Time frame: Baseline to 12 months follow-up.
Occurrence of Cardiac Safety Concern
Time frame: Baseline to 12 months follow-up.
Occurrence of Ototoxicity-Related Safety Concern
Time frame: Baseline to 12 months follow-up.
Occurrence of Hepatotoxicity-Related Safety Concern
Time frame: Baseline to 12 months follow-up.
Treatment Interruption
Time frame: Baseline to 12 months follow-up.
Treatment Discontinuation Proportion
Time frame: Baseline to 12 months follow-up.
Time to Treatment Discontinuation
Time frame: Baseline to 12 months follow-up.
All-Cause Mortality During 12-Month Follow-Up
Time frame: Baseline to 12 months follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Locked AMBER Version 1.0 methodological archive including disclosure document, protocol and statistical analysis plan, primary sample-size source code, and endpoint-level sample-size support matrix.Link provided by the sponsor.
- AMBER public preregistration through the Open Science Framework.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) underlying the reported AMBER trial results may be shared only upon reasonable scientific request and after approval by the principal investigator, Faculty of Medicine, Assiut University, and the relevant ethics committee or institutional authority where applicable. Shared data will exclude directly identifiable participant information and will be limited to variables necessary for the approved scientific purpose. The AMBER protocol, statistical analysis plan (SAP), informed consent form (ICF), and related methodological materials remain governed by the institutional and investigator approval process. Protected analytical code, model implementation materials, Bronchiectasis Assessment of Severity and Exacerbations (BASE) materials, and Bronchiectasis Phenotype Identification Model (BPIM) materials are not automatically shared with IPD and require separate written authorization.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ahmad M. Shaddad, MD principal investigator
Assiut University
Aliae M. Hussien, MD principal investigator
Assiut University
Maiada K. Hashem, MD principal investigator
Assiut University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard Bronchiectasis Care and Azithromycin in people with Non-cystic Fibrosis Bronchiectasis and Bronchiectasis Adult, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ahmad M Shaddad, MD (+201111171930, shaddad_ahmad@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of at Least One Bronchiectasis Exacerbation During 12-Month Follow-Up (time frame: Baseline to 12 months follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.