Date

2024-05-27

Protocol

Protocol changed

Item Changed

Secondary outcome(s) - Time of assessment(s)

Previous Version

• COPD exacerbation rate (annualised) [Baseline to 24 months]; • Time to first moderate-severe COPD Exacerbation [Baseline to 24 months]; • Severe (hospital admission) COPD exacerbation rate (annualized) [Baseline to 24 months]; • Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE [Baseline to 24 months]; • Quality of life assessed by St George's Respiratory Questionnaire (SGRQ) [Baseline to 24 months]; • EuroQoL Group 5-5 Dimension self-report questionnaire (EQ-5D-5L) [Baseline to 24 months]; • Healthcare utilisation costs and Quality Adjusted Life Years (QALYs) evaluation of the treatment intervention [Baseline to 24 months]; • Health status assessed by COPD Assessment Test (CAT) [Baseline to 24 months]; • Clinic spirometry: post-bronchodilator FEV1 (Forced Expiratory Volume) (L) [Baseline to 24 months]; • Clinic spirometry: % predicted post-bronchodilator. [Baseline to 24 months]; • Hospital admissions for all respiratory causes [Baseline to 24 months]; • Hospital admissions for all cardiac causes [Baseline to 24 months]; • Total Number of cardiac events [Baseline to 24 months];

Next Version

Time of assessment is from baseline to 24 months for: a) Time to a composite outcome (includes any) of: i. All-cause mortality ii. Hospitalisation for COPD exacerbation iii. Hospitalisation for primary cardiac cause (ischaemia, arrhythmia or heart failure [HF]) iv. MACE; b) COPD exacerbation rate (annualised) Exacerbations will be defined as worsening respiratory symptoms resulting in treatment with antibiotics or systemic glucocorticoids. Exacerbation severity will be graded (secondary outcome) according to the following scale: i. moderate (requiring oral corticosteroids [OCS], antibiotics or both without hospital admission) ii.severe (requiring above treatment and hospital admission); c) Time to first moderate-severe COPD exacerbation; d) Severe (hospital admission) COPD exacerbation rate (annualised); e) Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE; f) Quality of life assessed by St. George’s Respiratory Questionnaire (SGRQ); g) EuroQoL Group 5-Dimension self-report questionnaire, 5-Level version (EQ-5D-5L) to assess health state utilities; h) Cost-effectiveness of the treatment intervention; i) Health status assessed by COPD Assessment Test (CAT); j) Clinic spirometry: post-bronchodilator FEV1 (L) and percent (%) predicted; k) Hospital admissions for all respiratory causes; l) Hospital admissions for all cardiac causes; m) Total number of cardiac events: MACE plus acute arrhythmia, non-ST segment-elevated myocardial infarction (NSTEMI), urgent revascularization (stent/ angioplasty/ coronary artery by pass graft [CABGs]) and clinically diagnosed HF episodes.