An investigation into the effect of inhaled combined BUD/GLY/FORM on platelets in COPD as a potential cardioprotective mechanism: an exploratory, single-centre, investigator-blind, randomised controlled cross-over trial
Chronic Obstructive Airways Disease [COPD]
COPD CardioProtect is an exploratory, single-centre, laboratory-blind, randomised controlled cross-over trial of inhaled trial IMP on platelet reactivity and function in patients with COPD. The trial will compare the trial IMP is Budesonide 160 micrograms, Glycopyrronium bromide 9 micrograms and Formoterol fumarate dihydrate 5 micrograms in the Aerosphere device to be taken 2 inhalations twice daily [BUD/GLY/FORM also known as Trixeo Aerosphere] with the comparator medication of inhaled Glycopyrronium bromide 9 micrograms and Formoterol fumarate dihydrate 5 micrograms in the Aerosphere device to be taken 2 inhalations twice daily [GLY/FORM also known as Bevespi Aerosphere]. All participants will be issued with a SABA reliever [Salamol CFC-Free pMDI: Salbutamol sulfate 100 microgams] alongside their allocated study treatment to be taken 1-2 inhalations as required for relief of symptoms related to bronchospasm in COPD, up to a maximum of 8 inhalations in 24-hours. All participants will receive both trial IMP and comparator medications during the trial. The order of treatments will be randomly allocated using an online tool embedded within the study database in a 1:1 ratio as follows: A) GLY/FORM (run-in) for 4 weeks; BUD/GLY/FORM (Phase 1) for 4 weeks; GLY/FORM (wash-out) for 4 weeks; GLY/FORM (Phase 2) for 4 weeks B) GLY/FORM (run-in) for 4 weeks, GLY/FORM (Phase 1) for 4 weeks, GLY/FORM (wash-out) for 4 weeks, BUD/GLY/FORM (Phase 2) for 4 weeks The trial will recruit 40 participants with COPD from a single centre with each participant remaining in the trial for 16 weeks.
Current inclusion criteria as of 07/04/2025: 1. Males and females aged ≥40 years old 2. Primary respiratory diagnosis of COPD 3. FEV-1 <80% predicted and FEV-1/FVC <0.7 at screening (Spirometry does not need to be repeated at screening if quality assured spirometry has been completed and is available within the 3 months prior to consent being obtained if contraindicated) 4. Current or former smoker with at least 10 pack year smoking history 5. Able to demonstrate adequate inhaler technique with a pMDI inhaler and willing to take study medications as instructed 6. ≥1 moderate and/or ≥1 severe exacerbation of COPD (AECOPD) within the 12 months prior to recruitment* 7. Willing to undertake study procedures and assessments 8. Provided written informed consent * A moderate exacerbation is classified as an AECOPD treated with oral antibiotics and/or corticosteroids without ED attendance and/or hospitalisation. A severe AECOPD is one that requires ED attendance and/or hospitalisation Previous inclusion criteria: 1. Males and females aged ≥40 years old 2. Primary respiratory diagnosis of COPD 3. FEV-1 <80% predicted and FEV-1/FVC <0.7 at screening 4. Current or former smoker with at least 10 pack year smoking history 5. Able to demonstrate adequate inhaler technique with a pMDI inhaler and willing to take study medications as instructed 6. ≥2 moderate and/or ≥1 severe exacerbation of COPD (AECOPD) within the 12 months prior to recruitment* 7. Willing to undertake study procedures and assessments 8. Provided written informed consent * A moderate exacerbation is classified as an AECOPD treated with oral antibiotics and/or corticosteroids without ED attendance and/or hospitalisation. A severe AECOPD is one that requires ED attendance and/or hospitalisation
1. Other significant respiratory condition felt to be the primary cause for the patients symptoms and/or exacerbations (e.g. predominant asthma, bronchiectasis or interstitial lung disease) 2. Exacerbation of COPD requiring oral steroids and/or antibiotics within the 4 weeks prior to recruitment 3. Unstable vascular disease (e.g. unstable angina, acute myocardial infarction), cerebrovascular event (transient ischaemic attack or stroke), peripheral vascular disease (symptomatic intermittent claudication, critical limb ischaemia) within 3 months of screening. 4. Venous thromboembolic event (e.g. deep vein thrombosis or pulmonary embolism) within 3 months of screening 5. Treatment with 1 or more medication that will impact outcome measure assessment (e.g. clopidogrel, ticagrelor etc). *low dose Aspirin therapy will be permissible if taken at a stable dose throughout the study 6. Taking an inhaled corticosteroid (ICS) prior to study entry with a blood eosinophil count ≥0.3 x 10^9 per litre during the screening visit 7. (This criterium has been included to avoid risk to patients from ICS withdrawal during run-in and wash-out periods for patients considered to have required ICS by a clinician prior to study entry and with evidence of steroid responsive disease [Eos ≥0.3 x 10^9/L]) 8. Known allergy/sensitivity to study medications 9. Current participation in another interventional clinical study within 30-days or, if involving an Investigational Product, 5-half-lives, whichever is longer 10. For women of child bearing potential only - currently pregnant, breast feeding, or planned pregnancy during the study or not using acceptable contraception, as judged by the investigator