A trial looking at the use of bronchodilator and steroid inhalers for preventing flare ups of bronchiectasis

INTERVENTION: Participants will be randomised to one of the three trial groups in a 2:2:1 ratio to receive either dual therapy (LAMA/LABA), triple therapy (ICS/LAMA/LABA) or placebo: 1. Anoro Ellipta dry powder inhaler (LAMA/LABA ‐ 55 micrograms umeclidinium and 22 micrograms vilanterol) 2. Trelegy Ellipta dry powder inhaler (ICS/LAMA/LABA ‐ 92 micrograms fluticasone furoate, 55 micrograms umeclidinium and 22 micrograms vilanterol) 3. Placebo (matched placebo dry powder inhaler) Participants will use the trial inhaler once a day for 12 months and will have four additional hospital visits over the 12 months. They will have a telephone call every month to check that they have received their replacement inhaler through the post and will be asked to complete an exacerbation diary each week for 12 months to record any bronchiectasis exacerbations. CONDITION: Bronchiectasis ; Respiratory ; Bronchiectasis PRIMARY OUTCOME: ; Primary outcome measure:; Number of bronchiectasis exacerbations requiring treatment with antibiotics during 12 month treatment period as measured using participant reports and completed weekly exacerbation diary; ; Primary economic outcome measure:; 1. Cost per QALY at 12 months: costs based on the cost of the interventions, use of health services via a Participant Cost questionnaire administered at 1, 6 and 12 months post‐randomisation and adverse events; 2. QALYs measured via the EQ‐5D‐5L at baseline, 1, 6 and 12 months post‐randomisation; INCLUSION CRITERIA: 1. Adult patients with CT scan confirmed bronchiectasis and bronchiectasis is the predominant primary respiratory disease in the view of the investigator (CT images / CT reports must be available to complete radiological scoring for BSI) 2. History of 3 or more exacerbations in the preceding 12 months requiring antibiotics and/or steroids 3. Evidence of airflow limitation with an FEV1/FVC ratio less than 0.7 and/or daily mucus expectoration 4. Have less than 20 pack‐year history of smoking 5. Willing to have baseline treatment altered / ICS etc. stopped if already taking 6. Stable for 4 weeks prior to baseline 7. Stable dose of oral steroid for 4 weeks prior to baseline (only applicable for patients taking oral steroid as part of standard care) SECONDARY OUTCOME: ; 1. Number of hospital admissions for bronchiectasis exacerbations during 12 month treatment period, as measured using participant reports and completed weekly exacerbation diary and verified where possible by hospital discharge summary/HES data; 2. Time to first exacerbation of bronchiectasis as measured using participant reports/completed weekly exacerbation diary; 3. Number of emergency hospital admissions (all‐cause) as ascertained from primary care records at 1, 6 and 12 months visits and where needed; 4. Number of adverse events/drug reactions and cessation of treatment as reported by the participant to the research team or at 1, 6 and 12 months visits; 5. Health status measured using SGRQ (St Georges Respiratory questionnaire) and bronchiectasis specific quality of life measured using QOL‐B (quality of life ‐ bronchiectasis) at baseline, 1, 6 and 12 months visits; 6. Health‐related quality of life measured using EQ‐5D‐5L at baseline, 1, 3, 6 and 12 months visits; 7. Breathlessness measured using BDI (baseline dyspnoea index) at baseline; 8. Breathlessness measured using TDI (transition dyspnea index) at 1, 6 and 12 months visits; 9. Post bronchodilator lung function (LABA within 8 hours, short‐acting beta2 agonist within 2 hours) as measured by spirometry performed to ATS/ERS standards at baseline, 1, 6 and 12 month visits:; 9.1. Forced expiratory volume in 1 second (FEV1); 9.2. Forced vital capacity (FVC); 10. All‐cause, respiratory and cardiac mortality measured using Office of National Statistics data at 12 months; 11. Incremental cost per exacerbation avoided measured using Patient Cost Questionnaire at baseline, 1, 6 and 12 months; 12. Costs to the NHS and patients and lifetime cost‐effectiveness based on extrapolation modelling at 12 months; 13. Rates of radiologically confirmed pneumonia, compared to participant’s normal baseline measured by asking participants at 1, 6 and 12 months; ; Exploratory measures:; Eosinophil count measured as the number of cells per microliter of blood and categorised as low ‐ normal (0‐150/mm3) and normal ‐ high (>150/mm3) at baseline as both a single measure at that point and a median eosinophil level (median of last three available recordings when not on oral steroids);