Bronchiectasis Respiratory
Conditions
Interventions
Participants will be assigned in a 1:1 ratio to receive eradication treatment plus background therapy or background therapy only. Participants will be allocated to an arm using a minimisation algorith
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Adults (18 years or older) 2. Able to provide informed consent. 3. Capable of complying with all trial procedures and of completing the trial, in the opinion of the investigator. 4. Bronchiectasis, confirmed by computed tomography (CT), showing bronchiectasis in 1 or more lobes (a historical radiology report or report from the investigator confirming bronchiectasis is sufficient for enrolment) and the appropriate clinical syndrome (symptoms of cough, sputum production and/or respiratory tract infections). 5. Able to be prescribed one of the inhaled antibiotics defined in the intervention arm, in the opinion of the investigator. 6. P. aeruginosa infection confirmed by: 6.1. New isolation of P. aeruginosa, defined as the first documented sputum or other respiratory tract sample e.g. bronchoalveolar lavage samples) positive for P. aeruginosa within the 6 months prior to randomisation OR 6.2. New isolation of P. aeruginosa, within the 6 months prior to randomisation, following previous clearance of P. aeruginosa defined as a minimum of 12 months without a positive P. aeruginosa culture and at least 2 intervening cultures negative for P. aeruginosa.
Exclusion criteria
Exclusion criteria: 1. Current treatment with inhaled antibiotics or treatment with inhaled antibiotics within the previous 6 months 2. Chronic P. aeruginosa infection defined as isolation of P. aeruginosa persistently in sputum, or the absence of negative sputum samples for P. aeruginosa so that inclusion criteria (6) above cannot be met 3. Cystic fibrosis 4. Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. Current enrolment in non-interventional, observational studies will be allowed 5. Currently pregnant or breastfeeding 6. Unstable comorbidities (e.g., cardiovascular disease, active malignancy) which in the opinion of the investigator would make participation in the trial not in the participant’s best interest 7. Estimate eGFR <30 or abnormal liver function tests that in the opinion of the investigator make antibiotic treatment inappropriate (note that the trial is designed to be pragmatic and embedded within normal practice therefore testing is at the discretion of the managing clinician) 8. A strong preference, either from the managing clinician or the participant, for one of the two trial arms such that in the opinion of the investigator adherence to the trial protocol would not be possible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of pulmonary exacerbations (EMBARC definition) from day 0 to week 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cost-effectiveness of P. aeruginosa eradication treatment compared with standard care, measured from day 0 to week 104 using: 1.1. Frequency of pulmonary exacerbations (EMBARC definition) 1.2. Incremental cost per exacerbation prevented 1.3. Incremental cost per quality adjusted life year (QALY) gained 2. Frequency of P. aeruginosa isolation in sputum samples measured using sputum microbiology at day 0, weeks 12, 52, 104 3. Hospitalisations for severe exacerbations recorded using medical records from day 0 to week 104 4. Quality of life measured using the Quality of Life-Bronchiectasis (QOL-B) respiratory symptom scale, Chronic Airways Assessment Test (CAAT) and EQ-5D-5L on day 0, weeks 12, 52, 104 and the Bronchiectasis Exacerbation and Symptom Tool (BEST) diary daily day 0 to week 104 5. Time to reinfection (isolation of P. aeruginosa after a first negative sputum sample) from Day 0 to week 104 6. Total days of antibiotic use recorded using prescribing medical records from Day 0 to week 104 7. P. aeruginosa antibiotic resistance measured using sputum microbiology at day 0, weeks 12, 52, 104 8. All-cause healthcare contacts recorded using medical records from day 0 to week 104 9. All-cause mortality recorded using medical records from day 0 to week 104 10. Treatment adherence recorded using patient report from day 0 to week 104 11. Frequency of adverse events (AEs) and serious adverse events (SAEs) recorded using medical records & participant reporting from day 0 to week 104 12. Time to commencement of long term inhaled antibiotic treatment recorded using prescribing medical records from day 0 to week 104 Exploratory Objectives: P. aeruginosa abundance measured by molecular laboratory tests at day 0, weeks 12, 52, 104 | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactGillian Martin
Outcome results
None listed