Chronic obstructive pulmonary disease (COPD) with widening of the air tubes (bronchiectasis) Respiratory Chronic Obstructive Pulmonary Disease (COPD) with associated bronchiectasis
Conditions
Interventions
This is an open label randomised trial. 80 patients with COPD and coexistent bronchiectasis to be recruited with 40 patients in each arm. one arm would receive triple therapy of inhalers (inhaled cort
Sponsors
The University of Edinburgh & Lothian Health Board
Eligibility
Sex/Gender
All
Age
40 Years to 100 Years
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Informed Consent: A signed and dated written informed consent prior to study participation. 2. Type of subject: Outpatient. 3. Age: Subjects 40 years of age or older at screening visit. 4. Gender: Male or female subjects. 5. COPD Diagnosis: An established clinical history of COPD as documented in medical notes in accordance with the definition by the American Thoracic Society/European Respiratory Society. COPD-Bronchiectasiscoexistence: smoking history of greater than 10 pack year, with a post bronchodilator FEV1/FVC ratio 10 pack-years at screening (visit 1) [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or cigar use cannot be used to calculate pack-year history.
Exclusion criteria
Exclusion criteria: 1. Pregnancy: Women who are pregnant or breast feeding or are planning on becoming pregnant during the study. 2. Asthma: Subjects with a current/ concurrent diagnosis of asthma. 3. a1-antitrypsin deficiency: Subjects with known a1-antitrypsin deficiency as the underlying cause of COPD. 4. Other respiratory disorders: Subjects with active tuberculosis, active lung cancer, sarcoidosis, lung fibrosis, pulmonary hypertension, or other interstitial lung diseases. 5. Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening. 6. Risk Factors for Pneumonia: immune suppression (e.g. HIV, Lupus) or other risk factors for pneumonia, when patients are on long standing immunosuppressive drugs or have neuromuscular conditions affecting control of the upper airway, such as Parkinson’s disease, Motor Neuron Disease or Myasthenia Gravis. 7. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). In addition, any subject that experiences pneumonia and/or moderate or severe COPD exacerbation during the washout period will be excluded. 8. Other Respiratory tract infections that have not resolved at least 7 days prior to screening including COVID19 infections 9. Other diseases/abnormalities: Subjects with historical or current evidence of any of the following clinically significant abnormalities that are uncontrolled: 9.1. cardiovascular 9.2. neurological 9.3. psychiatric (including documented psychiatric reactions or hypersensitivity to oral steroids) 9.4. renal 9.5. hepatic 9.6. immunological 9.7. gastrointestinal 9.8. urogenital (e.g. significant prostatic hyperplasia/bladder outflow obstruction) 9.9. nervous system 9.10. musculoskeletal (including known significant osteoporosis) 9.11. skin 9.12. sensory 9.13. endocrine (including uncontrolled Type 1 or 2 diabetes or thyroid disease) 9.14. ocular (e.g. significant narrow angle glaucoma) 9.15. haematological 10. Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, oesophageal or gastric varices or persistent jaundice. 11. Unstable or life-threatening cardiac disease 12. Abnormal and clinically significant 12-Lead ECG finding 13. Other Contraindications: A history of allergy or hypersensitivity to any oral steroid or corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, uncontrolled symptomatic prostatic hypertrophy or bladder neck obstruction that, in the opinion of the Investigator contraindicates study participation. 14. Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, prostrate carcinoma, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5year waiting period if the subject has been considered cured by treatment. 15. Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3L/min (Oxygen use up to 3L/min flow is not exclusionary.) 16. Medication prior to spirometry: Subjects who are medically unable to withhold their salbutamol for the 4-hour period required prior to spirometry testing at each study visit. 17. Pulmonary rehabilitation: Subjects who have participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A baseline to 1-year change (expressed in log units) in colony forming units per ml between treatment arms (LABA-LAMA plus corticosteroid versus LABA-LAMA only) measured via sputum samples taken at baseline, 6 months & 12 months between the 2 arms of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in sputum microbial diversity and microbial biomass (see analyses below for details) between the two arms. measured via sputum samples taken at baseline, 6 months & 12 months 2. Sputum colour as assessed by a standardised colour chart- patients are graded as mucoid (clear or grey phlegm, muco-purulent (light yellow or green) and purulent (dark yellow or green) measured via sputum samples taken at baseline, 6 months & 12 months 3.1. Microbial community composition (gram negative/positive ratio, abundance of potential pathogens etc.) measured via sputum samples taken at baseline, 6 months & 12 months 3.2. Fungal microbiome: between the two groups to see if ICS can influence the heterogeneity of the fungal community in terms of absolute and relative abundance. measured via sputum samples taken at baseline, 6 months & 12 months 4. Spirometry: forced expired volume in 1 second, forced vital capacity and its ratio and mid expiratory flows (FEF25-75) (attenuation of decline in lung function would be of long-term benefit to patients if found). Measured using spirometry at screening and consenting visit, baseline, 6 months & 12 months 5. Quality of Life: quality of life assessed by the COPD Assessment Tool (CAT) and St. Georges Respiratory Questionnaire. Breathlessness is included as part of this questionnaire. Questionnaires completed at baseline, 6 months & 12 months and at exacerbation visits 6. Sputum inflammation: we will assess sputum myeloperoxidase as a measure of neutrophil burden and free elastase activity. measured via sputum samples taken at baseline, 6 months & 12 months 7. Serum inflammation: we will measure white cell count and differential, erythrocyte sedimentation rate (ESR), C Reactive Protein (CRP) and intercellular adhesion molecule 1 (ICAM-1) Previous research has shown that at high bacterial loads there is increased ICAM-1 Measured via blood tests at baseline, 6 months & 12 months 8. Exacerbations: These would be categorised as *time to the | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactGourab Choudhury
Outcome results
None listed