Microbiome Use to Stratify Use of Inhaled Corticosteroids: MUSIC Trial (MUSIC)
Chronic Obstructive Pulmonary Disease
About this trial
This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease focused on measuring Chronic Obstructive Pulmonary Disease
Eligibility Criteria
Inclusion Criteria:
- Male and female patients aged greater than or equal to 40 years
- Current or ex smokers having at least a 10 pack year smoking history
- A clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) made by a physician with a post-bronchodilator forced expiratory volume 1 (FEV1)/ forced vital capacity (FVC) ratio at screening of <70%
- Severe COPD according to consensus guidelines consisting of a post-bronchodilator FEV1 <50% predicted at screening and/or a history of 2 or more exacerbations in the previous year OR one hospital admission for an exacerbation of COPD in the previous year (equivalent to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 grade C and D)
- Able to perform all study procedures including spirometry and questionnaires with minimal assistance.
Exclusion Criteria:
- Inability to give informed consent
- Asthma (defined according to Scottish Intercollegiate Guidelines Network)
- A primary diagnosis of bronchiectasis confirmed on high-resolution computed tomography.(it is not necessary to perform a computerised tomography (CT) scan to exclude this if the patient has not previously had one. Only known bronchiectasis with a previous CT scan should be excluded).
- • Antibiotics within the past 28 days, apart from oral macrolides which are permitted if they have been used for at least 3 months prior to randomization
- Oral/ nasal corticosteroids of any kind in the 28 days prior to screening visit
- Current use of the following: roflumilast, ritonavir, itraconazole, telithromycin, or ketoconazole (or other CYP3A4 inhibitors).
- Active, or within 28 days of screening visit, oral candidiasis, actively receiving dental treatment for oral infection or poor dentition.
- Immunosuppression including current oral corticosteroids at a dose >5mg for >28 days.
- Glomerular filtration rate (eGFR) below 30ml/min/1.73meter squared or requiring dialysis. Last known eGFR result will be used .
- Use of any investigational drugs within five times of the elimination half-life after the last study dose or within 30 days, whichever is longer.
- Known allergy, intolerance or contraindication to any of the study drugs
- Galactose intolerance
- Unstable co-morbidities (cardiovascular disease, active malignancy) which in the opinion of the Investigator would make the patient unsuitable to be enrolled in the study. This includes any abnormality identified on screening bloods or screening electrocardiograph which in the opinion of the Investigator would make the patient unsuitable for the study.
- An exacerbation of COPD occurring during the screening to randomisation period. If this occurs the patient should be withdrawn from the study and may be rescreened once they have been free from corticosteroid and antibiotic treatment for 28 days. In these cases patients would receive the current Participant Information Sheet and be consented prior to starting the study from Visit 1.
- Documented that the patient has never received pneumococcal polysaccharide vaccination
- Receipt of Pneumococcal conjugate vaccine (e.g PCV-13)
- Pregnancy or breast feeding
- Women of child bearing potential (WOCBP) who are not practicing an acceptable method of contraception (see below)
Acceptable forms of contraception:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system ( IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
Sites / Locations
- NHS Tayside
- Blackpool Teaching Hospital NHS Foundation Trust
- NHS Lothian
- NHS Greater Glasgow and Clyde
- NHS Fife
- NHS Lanarkshire
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Active Comparator
Active Comparator
1: Symbicort 400/12 & Eklira Genuair
2: Seretide 500/50 & Eklira Genuair
3: Seretide 250/50 & Eklira Genuair
4: Duaklir Genuair
Budesonide 400mcg & formoterol fumarate 12mcg: 1 inhalation twice daily, inhalation powder and Aclidinium bromide 322mcg: 1 inhalation twice daily, inhalation powder for 3 months
Fluticasone propionate 500mcg & salmeterol 50mcg: 1 inhalation twice daily, inhalation powder and Aclidinium bromide 322mcg: 1 inhalation twice daily, inhalation powder for 3 months
Fluticasone propionate 250mcg & salmeterol 50mcg: 1 inhalation twice daily, inhalation powder and Aclidinium bromide 322mcg: 1 inhalation twice daily, inhalation powder for 3 months
Aclidinium bromide 340mcg & formoterol fumarate 12mcg: 1 inhalation twice daily, inhalation powder for 3 months