Chronic Obstructive Pulmonary Diseae MedDRA version: 20.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Duaklir Genuair
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: aclidinium bromide
CAS Number: ?320345-99-1
Conc
Sponsors
University of Dundee & NHS Tayside
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female patients aged > 40 years • Current or ex smokers having at least a 10 pack year smoking history • A clinical diagnosis of COPD made by a physician with a post-bronchodilator FEV1/FVC ratio at screening of =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Inability to give informed consent • Asthma (defined according to Scottish Intercollegiate Guidelines Network criteria) [29])# • A primary diagnosis of bronchiectasis confirmed on computed tomography.(it is not necessary to perform a 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 strong 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/1.73m2 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 ECG 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effects of the inhaled corticosteroids fluticasone propionate/salmeterol 500/50 mcg vs budesonide/formoterol 400/12 mcg on upper airway bacterial load from throat swabs.; Secondary Objective: To determine the effects of the inhaled corticosteroids fluticasone propionate/salmeterol 500/50 mcg vs budesonide/formoterol 400/12 mcg on lower airway bacterial load and microbiome from sputum and on upper airway in nasal swab To compare the effects of fluticasone/salmeterol 250/50mcg vs budesonide/formoterol 400/12 mcg on upper and lower airway microbiome in throat/nasal and sputum samples. To compare the effects on the upper and lower airway microbiome in throat, nasal swabs and sputum of individual inhaled corticosteroids (ICS) fluticasone propionate and budesonide compared to a dual bronchodilator based regime without ICS To compare the impact of high and low dose inhaled corticosteroid fluticasone propionate on the upper and lower airway microbiome in throat, nasal swabs and sputum To determine the combined impact of inhaled corticosteroids on bacterial load in upper and lower airway using throat swabs, nasal swabs and sputum compared to dual bronchodilator regime. In thi ;Primary end point(s): Bacterial load of total respiratory pathogens determined by quantitative polymerase chain reaction. Continuous variable at 0, 1, 2 and 3 months;Timepoint(s) of evaluation of this end point: Continuous variable at 0, 1, 2 and 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the effects of the inhaled corticosteroids fluticasone propionate/salmeterol 500/50 mcg vs budesonide/formoterol 400/12 mcg on lower airway bacterial load and microbiome from sputum and on upper airway in nasal swab To compare the effects of fluticasone/salmeterol 250/50mcg vs budesonide/formoterol 400/12 mcg on upper and lower airway microbiome in throat/nasal and sputum samples. To compare the effects on the upper and lower airway microbiome in throat, nasal swabs and sputum of individual inhaled corticosteroids (ICS) fluticasone propionate and budesonide compared to a dual bronchodilator based regime without ICS To compare the impact of high and low dose inhaled corticosteroid fluticasone propionate on the upper and lower airway microbiome in throat, nasal swabs and sputum To determine the combined impact of inhaled corticosteroids on bacterial load in upper and lower airway using throat swabs, nasal swabs and sputum compared to dual bronchodilator regime. In this analysis, results from all ICS arms will be pooled. To evaluate the impact of inhaled corticosteroids on airway and systemic inflammation To evaluate the safety and tolerability of withdrawal of inhaled corticosteroids in severe COPD To evaluate if changes in the airway microbiota are associated with AE’s To determine the impact of ICS withdrawal on airway bacterial load, airway microbiome and airway inflammation. ;Timepoint(s) of evaluation of this end point: Continuous variable at 0, 1, 2 and 3 months | — |
Countries
United Kingdom
Contacts
Public ContactJames Chalmers
University of Dundee
Outcome results
None listed