Bronchiectasis Respiratory Bronchiectasis
Conditions
Interventions
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 inh
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 05/09/2022: 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 2 or more exacerbations in any 12-month period in the preceding 2 years 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 either: 4.1. Less than 20 pack-year history of smoking OR 4.2. Greater than 20 pack-year history of smoking with an FEV1 >79% predicted (to exclude COPD) 5. For patients taking ICS, LAMA or LABA treatment prior to recruitment, willing to have these treatments changed or stopped 6. Stable bronchiectasis with no exacerbations 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) _____ Previous 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)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 05/09/2022: 1. Cystic fibrosis-related bronchiectasis 2. Where bronchiectasis is not the main disease or there are contraindications to ICS withdrawal 3. Predominant COPD or asthma. (Patients who have a historical diagnosis of asthma and/or COPD but where the investigator has sufficient evidence to refute these diagnoses can still be included. This is to be documented in the source and the CRF.) 4. Indication to remain on ICS (e.g. asthma, COPD, allergic bronchopulmonary aspergillosis, inflammatory bowel disease) or known intolerance to any of the trial drugs or their ingredients 5. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Inability to perform spirometry or quality of life questionnaires 7. Patients who are: 7.1. Pregnant 7.2. Breastfeeding 7.3. Of childbearing potential with a positive urine pregnancy test prior to starting trial IMP 7.4. Male or female of childbearing potential unwilling to use contraception throughout the trial (postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential). 8. Anyone with cognitive impairment who may not be able to consent 9. Those who do not speak English or cannot comply with trial procedures 10. Any potential participant who the investigator believes will not be able to complete the study visits and procedures 11. A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, ß2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation 12. Use of acute antibiotics or systemic steroids within 4 weeks of baseline 13. Malignancy diagnosed within 5 years of the first trial medication administration where the investigator feels the trial may be affected by recurrence or progression of the malignancy (e.g. patients with stable breast cancer, current prostate cancer or 'expected curative' cancer surgery may not be excluded at the investigator's discretion) 14. Administration of an investigational agent within 30 days of first dose of trial medication _____ Previous exclusion criteria: 1. Cystic fibrosis related bronchiectasis 2. Where bronchiectasis is not the main disease or there are contraindications to ICS withdrawal 3. Predominant COPD or asthma (Patients who have a historical diagnosis of asthma and/or COPD but where the investigator has sufficient evidence to refute these diagnoses can still be included. This is to be documented in the source and the CRF) 4. Indication to remain on ICS (e.g. asthma, COPD, allergic bronchopulmonary aspergillosis, inflammatory bowel disease) or known intolerance to any of the trial drugs or their ingredients 5. Inability to perform spirometry or quality of life questionnaires 6. Patients who are: 6.1. Pregnant 6.2. Breastfeeding 6.3. Of childbearing potential with a positive urine pregnancy test prior to starting trial IMP 6.4. Male or female of childbearing potential unwilling to use contraception throughout the trial (postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential). 7. Anyone with cognitive impairment who may not be able to consent 8. Those who do not speak English or cannot comply with trial procedures 9. Any potential partici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 17/05/2023: 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 Health Care Utilisation 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 3. Transport and time for participants to utilise health care appointments will be assessed via the Time and Travel Questionnaire administered at 12 months post-randomisation Previous primary outcome measure: 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 17/05/2023: 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. Hospitalisation due to bronchiectasis exacerbation data collected up to 24 months after visit 1: screening/baseline, will be used to extend modelling beyond 12 months as a sensitivity analysis. 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 at 1, 6 and 12 months visits and from primary care records 4. Number of serious adverse events as a result of drug reactions or reactions to the 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 as ascertained from Office of National Statistics data records of trial participants (collected up to 24 months after visit 1: screening/baseline) 11. Incremental cost per exacerbation avoided; costs based on the cost of the interventions (micro-co | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactHazel;Miranda Wilde;Morton
;
Outcome results
None listed