Chronic Obstructive Airways Disease [COPD] Respiratory
Conditions
Interventions
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
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 particip
Sponsors
Hull University Teaching Hospitals NHS Trust
Eligibility
Sex/Gender
All
Age
40 Years to 120 Years
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 07/04/2025: Change in platelet activation measured by P-selectin expression (unstimulated and following stimulation with escalating concentrations of ADP (and collagen-related peptide (CRP)) using FACs analysis following treatment with inhaled BUD/GLY/FORM compared with inhaled GLY/FORM measured at 16 weeks. Previous primary outcome measure: Change in platelet activation measured by P-selectin expression (unstimulated and following stimulation with escalating concentrations of ADP and collagen) using FACs analysis following treatment with inhaled BUD/GLY/FORM compared with inhaled GLY/FORM measured at 16 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measure as of 07/04/2025: Measured at 16 weeks: 1. Platelet-Monocyte Aggregate formation and platelet fibrinogen binding (unstimulated and following stimulation with escalating concentrations of ADP and collagen-related peptide (CRP)) following treatment with inhaled BUD/GLY/FORM compared with inhaled GLY/FORM. All other platelet markers/assays (below) will be evaluated before and after treatment with inhaled BUD/GLY/FORM compared with inhaled GLY/FORM. 2. Platelet-leucocyte interactions will be analysed using FACs: Whole blood will be stained with antibodies for CD45 for all white blood cells or CD14 (Monocytes) and CD16 (Neutrophils). CD41 will be used to identify platelets within these different populations to identify platelet-leucocyte aggregates. This will be completed in duplicate. 3. Additional markers of Platelet activity will be assessed using the following assays: 3.1. FACs: Platelet integrin IIb3 activation to escalating doses of different agonists (collagen-related peptide (CRP) and ADP) will be completed, in duplicate. 3.2. Platelet aggregation: Platelet responses to escalating doses of different agonists (collagen and ADP) will be completed. 3.3. Platelet spreading: This technique demonstrates how well platelets adhere and activate on various matrix proteins (fibrinogen and collagen). These proteins are either within the thrombus (fibrinogen) or within the extracellular matrix (collagen). 3.4. Seahorse Analyser (Metabolism): This process identifies how platelets use energy via glycolysis and oxidative phosphorylation in both basal conditions and after stimulation with platelet agonists such as Thrombin and collagen. 4. Additional clinical outcome measures will include: 4.1. Spirometry (FEV-1, FVC, FEV-1/FVC ratio) 4.2. CAT score 4.3. Cardiac biomarkers – high sensitivity troponin T, nt-proBNP Previous secondary outcome measures: Measured at 16 weeks: 1. Platelet-Monocyte Aggregate formation and platelet fibrinogen binding (u | — |
Countries
England, United Kingdom
Contacts
Public ContactHull Health Trials Unit
Outcome results
None listed