Date

2024-05-27

Protocol

Protocol changed

Item Changed

Primary outcome(s)

Previous Version

• All-cause mortality; • Hospitalisation for COPD exacerbation; • Hospitalisation for primary cardiac cause (ischaemia, arrhythmia or heart failure); • Major Adverse Cardiovascular Event (MACE); Major Adverse Cardiovascular Event (MACE) includes myocardial infarction, sudden death, cardiac death or a fatal event in system organ classes for cardiac and vascular disorders, and serious and non-serious stroke.

Next Version

The primary outcome will be a composite outcome of the following that will be categorised into a hierarchy according to clinical importance: • Death - any cause of death; • Severe COPD exacerbation -hospitalised and treated with OCS/Abx or both; • Hospitalisation with a primary cardiac cause - ischemia, arrythmia, or heart failure, or ischaemic stroke; • Moderate COPD exacerbation - not hospitalised but treated with OCS /Abx or both; • Cardiac Hospitalisation - hospitalisation for a cardiac cause other than ischemia, arrythmia or heart failure; • Respiratory Hospitalisation - hospitalisation for a respiratory cause other than COPD exacerbation; • Decrease in FEV1 or greatest FEV1 % drop - largest decrease in FEV1 from post-bronchodilator spirometry at baseline; • Mild COPD exacerbation - treated with increased inhalers / inhaler technique / addition of theophylline; • Higher SGRQ score at 12m and 24m (clinically important change > 4); • Higher CAT score at 12m and 24m (clinically important change >2); • It will be analysed using a win ratio approach, assessing the effect of the beta-blocker intervention against placebo for each outcome sequentially starting from the most clinically important (all-cause mortality) and finishing with the least important (CAT score).