Exacerbation and Symptom Control After Pseudomonas Eradication Treatment in Adult Bronchiectasis: a multicentre randomized controlled trial (ESCAPE)
Bronchiectasis
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 algorithm, with factors for centre, long-term use of macrolides, and first isolation vs new isolation following previous clearance. Intervention: P. aeruginosa eradication treatment consisting of systemic antibiotics (either oral or intravenous as clinically indicated) alongside or followed by inhaled anti-pseudomonal antibiotics for 3 months, in addition to background therapy. Comparator: Background therapy only. The intervention treatment will be prescribed as per British Thoracic Guidelines and following local clinician decision and usual practice. In the British Thoracic Guidelines, P. aeruginosa eradication treatment is defined as first line treatment with the oral antibiotic ciprofloxacin 500 mg or 750 mg twice a day for 2 weeks. Second line treatment of IV antipseudomonal beta-lactam ± an IV aminoglycoside for 2 weeks. This would be followed by a 3-month course of a nebulised antipseudomonal antibiotic. The protocol defines the eradication treatment options. Background therapy may consist of their existing bronchiectasis treatments such as airway clearance, bronchodilators, long term macrolide treatment or other symptomatic therapies e.g mucoactive drugs. Background therapy also includes administration of antibiotics if patients have symptoms of an exacerbation.
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.
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.