Date

2024-05-27

Protocol

Protocol changed

Item Changed

Secondary outcome

Previous Version

• 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, antibiotics or both without hospital admission) ii. severe (requiring above treatment and hospital admission; • Time to first moderate-severe COPD Exacerbation; • Severe (hospital admission) COPD exacerbation rate (annualized); • Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE; • Quality of life assessed by St George's Respiratory Questionnaire (SGRQ) The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. Psychometric testing has demonstrated its repeatability, reliability and validity. Sensitivity has been demonstrated in clinical trials. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. The SGRQ has been used in a range of disease groups including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis, and in a range of settings such as randomised controlled therapy trials and population surveys.; • EuroQoL Group 5-5 Dimension self-report questionnaire (EQ-5D-5L) to assess health state utilities EQ-5D-5L consists of 2pg: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). Five dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. Patient indicates their health state by ticking most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. EQ VAS records patient's self-rated health on a vertical visual analogue scale. Endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.; • Healthcare utilisation costs and Quality Adjusted Life Years (QALYs) evaluation of the treatment intervention Mean differences in healthcare utilisation costs and Quality Adjusted Life Years between both treatment groups will be estimated. Costs will be ascertained from participants and study records. Health care utilisation will be on the basis of self-reported GP and hospital attendances and changes in concomitant medication. Health state utilities will be estimated via the EQ-5D-5L and will be used to weight survival up to 24 months to determine Quality Adjusted Life Years.; • Health status assessed by COPD Assessment Test (CAT); • Clinic spirometry: post-bronchodilator FEV1 (Forced Expiratory Volume) (L); • Clinic spirometry: % predicted post-bronchodilator.; • Hospital admissions for all respiratory causes.; • Hospital admissions for all cardiac causes; All cardiac causes includes ischaemia, arrhythmia, heart failure, acute arrhythmia, non-ST-elevation myocardial infarction, urgent revascularization (stent/angioplasty/coronary artery bypass grafting), and MACE events (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); • Total Number of cardiac events: MACE plus acute arrhythmia, Non-ST-elevation myocardial infarction (NSTEMI), urgent revascularisation (stent/angioplasty/Coronary artery bypass grafting [CABGs]) and clinically diagnosed heart failure episodes

Next Version

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) 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 revascularisation (stent/angioplasty/coronary artery bypass graft [CABGs]) and clinically diagnosed HF episodes.