Medical condition: Bronchiectasis Medical condition in lay language: Bronchiectasis Therapeutic areas: Diseases [C] - Respiratory Tract Diseases [C08] Respiratory
Conditions
Interventions
The intervention is the continuation of long-term azithromycin compared to a matched placebo. The dose is matched to the patient's pre-existing long-term macrolide dose commonly 250mg once a day azith
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
16 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Age 16 years or older (no upper age limit) 2. Be able and willing to provide informed consent. 3. Have clinically stable Bronchiectasis, i.e. no Bronchiectasis exacerbation for at least 30 days. 4. Established clinical diagnosis of Bronchiectasis and prescribed receiving prophylactic azithromycin or an equivalent long-term macrolide for at least 90 days in the past 12 months to reduce risk of Bronchiectasis exacerbations 5. Historical CT scan report confirming bronchiectasis (or equivalent e.g. bronchogram) 6. Any suspected aetiology of Bronchiectasis can be included 7. Any treatment regimen of azithromycin or an equivalent long-term macrolide (noting current guidelines allow 250mg OD thrice weekly, 250mg each day or 500mg OD thrice weekly of azithromycin) 8. Available data (more than 5 parameters from the following routinely collected data) to calculate Bronchiectasis Severity Index (BSI) (1) age, 2) sex, 3) FEV1% predicted current or historical in last 12 months), 4) number of prior exacerbations, 5) prior hospitalisations in last 24 months, 6) MRC dyspnoea score, 7) microbiology status (Pseudomonas colonies or other) , 8) BMI. CT Reiff scoring also preferred but not essential. In addition to the main trial inclusion criteria: Participants who are able may choose to provide informed consent for the optional sub-study. This will be a separate consent question to tick on the consent form (for the feedback questionnaire only, or feedback questionnaire and possibility of telephone call to gain further in-depth feedback).
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to any of the trial drugs or excipients. 2. Current breast feeding, pregnancy or planned pregnancy during the trial. 3. Any medical history or clinically relevant abnormality that makes patient ineligible for inclusion because of a safety concern relating to continuing or discontinuing azithromycin or other considerations. 4. Bronchiectasis exacerbation requiring treatment with antibiotics and/or steroids up to 30 days prior to study enrolment (can be re-screened after 30 days). 5. Azithromycin prophylaxis prescribed for non-Bronchiectasis condition or as part of treatment regimen for Non-tuberculosis mycobacteria. 6. Azithromycin prophylaxis prescribed for <90 days. 7. Participation in other trial of investigational medicinal product of bronchiectasis (unless a co-enrolment agreement has been developed and approved). Participation in observational studies is allowed. 8. Where participant / supervising clinician does not feel at equipoise for randomisation to either continuation or withdrawal of macrolide. 9. Participant has usual regimen of azithromycin of winter on therapy/ summer cessation of therapy AND patient unwilling to be randomised to trial allocation for 12 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first exacerbation of bronchiectasis, as defined by a sustained increase in symptoms, usually of 72 hours, requiring antibiotic therapy measured using data collected from electronic case report forms (eCRF). The primary endpoint does not have a fixed time point of evaluation. The maximum treatment period is 12 months with further follow-up after trial allocation medication ends from 13-24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcome measures are assessed at 3, 6, 12, 18, and 24 months unless otherwise stated: 1. Further evaluation of clinical effectiveness, defined by the effect on exacerbations (specifically number/rate and severity of exacerbations) measured using data collected from eCRF 2. Health status as measured using the following tools for symptoms and quality of life: 2.1. EuroQol 5-Dimension 5-Level (EQ-5D-5L) 2.2. Quality of Life Bronchiectasis (QoLB) 2.3. Chronic Airways Assessment Tool (CAAT) 2.4. Visual Analog Scale (VAS) 2.5. Patient Health Questionnaire-2 (PHQ-2) 2.6. Generalized Anxiety Disorder-2 (GAD-2) 2.7. Clinical Frailty Score (CFS) 2.8. Self-Rated Health Scale (SRHS) 3. Hospitalisation and healthcare use measured using a Health Utilisation Questionnaire at 6, 12, 18, 24 months 4. Mortality (all-cause, respiratory, cardiac) measured using data collected from eCRF 5. Adverse events of special interest and serious adverse reactions measured using data collected from eCRF 6. Factors or patient subgroups that impact interventions measured using data collected from eCRF 7. To estimate the cost-effectiveness of complete discontinuation of azithromycin chemoprophylaxis in people with Bronchiectasis at high risk of exacerbations measured using a Health Utilisation Questionnaire 8. To evaluate adherence measured using pill counts at trial visits | — |
Countries
England, Scotland, United Kingdom, Wales
Outcome results
None listed