Azithromycin to Modify Bronchiectasis Exacerbation Risk

NCT07608328 | Not Yet Recruiting Phase 4 DMC

• 3 other identifiers: 2026-5-5110.5281/zenodo.2017896310.17605/OSF.IO/RE54V
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief 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). 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.

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); 12-month follow-up; Assiut University

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 12 months follow-up.

Secondary Outcomes (22)

• Number of Bronchiectasis Exacerbations During 12-Month Follow-Up

  Baseline to 12 months follow-up.

• Time to First Bronchiectasis Exacerbation

  Baseline to 12 months follow-up.

• Occurrence of at Least One Severe Bronchiectasis Exacerbation Requiring Hospitalization

  Baseline to 12 months follow-up.

• Occurrence of at Least One Bronchiectasis-Related Hospital Admission

  Baseline to 12 months follow-up.

• Time to First Severe Bronchiectasis Exacerbation Requiring Hospitalization

  Baseline to 12 months follow-up.

Other Outcomes (53)

• Proportion of Participants with Zero Bronchiectasis Exacerbations

  Baseline to 12 months follow-up.

• Proportion of Participants with Two or More Bronchiectasis Exacerbations

  Baseline to 12 months follow-up.

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

  Baseline to 12 months follow-up.

Study Arms (2)

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.

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.

Other: Standard Bronchiectasis Care; Drug: Azithromycin

Interventions

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.

Also known as: Routine bronchiectasis care

Experimental Azithromycin Arm; Placebo Control Arm

Azithromycin DRUG

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

Also known as: Azithromycin 250 mg

Experimental Azithromycin Arm

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.

Also known as: Matching placebo tablet

Placebo Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut university-Faculty of Medicine

Asyut, 71515, Egypt

Location

Related Links

• 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.
• AMBER public preregistration through the Open Science Framework.

MeSH Terms

Conditions

Bronchiectasis

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Ahmad M. Shaddad, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Aliae M. Hussien, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Maiada K. Hashem, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Alaa S. Ali

  Assiut University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmad M Shaddad, MD

CONTACT

+201111171930; shaddad_ahmad@aun.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: AMBER is a double-blind, placebo-controlled randomized trial. Participants, care providers, investigators, and outcomes assessors will remain unaware of participant-level treatment assignment until database lock unless emergency unblinding is required for participant safety. Matching placebo will be prepared to resemble active azithromycin as closely as feasible in appearance, packaging, and administration schedule. Study medication will be dispensed using concealed allocation and sequentially numbered containers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: May 27, 2026
• Study Start: May 21, 2026
• Primary Completion (Estimated): June 21, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after publication of the primary AMBER trial results and for 3 years thereafter.
• Access Criteria: Access may be granted to qualified researchers who submit a methodologically sound proposal related to non-cystic fibrosis bronchiectasis (NCFB), bronchiectasis exacerbation prevention, macrolide therapy, randomized trial methodology, longitudinal clinical outcomes, or respiratory translational research. Requests require written approval from the principal investigator, Faculty of Medicine, Assiut University, and the relevant ethics committee or institutional authority where applicable. Approved requesters must sign a data use agreement covering confidentiality, restricted scientific use, secure data storage, no re-identification, no unauthorized redistribution, no commercial use, proper acknowledgement, and compliance with ethical and institutional regulations. Analytical code, protected implementation materials, BASE materials, BPIM materials, and other intellectual materials require separate written authorization.

Locations

EG (1)