Preventing Adverse Cardiac Events in Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 280
- 试验地点
- 24
- 主要终点
- All-cause mortality
研究概览
简要总结
A double-blind, randomised controlled trial in participants with COPD to assess the efficacy of proactive treatment of cardiac risk in people with COPD. We hypothesise that treating known and undiagnosed CVD in COPD participants will improve both cardiac and respiratory outcomes.
详细描述
Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global health-related morbidity and mortality. Heart disease in COPD is a known but neglected comorbidity and cardiovascular disease (CVD) accounts for 30-50% of deaths in COPD participants. Studies repeatedly show that CVD in COPD participants is under-recognised and under-treated yet participants with COPD are frequently excluded from clinical trials of drugs which reduce cardiac morbidity and mortality. This has led to under-treatment of CVD in COPD participants. A particular concern is low use of β-blockers. These have previously been considered to be contra-indicated in COPD and no RCTs have been conducted in this population. There is now observational evidence that cardioselective β-blockers are safe and may improve mortality, but this data is limited to retrospective analyses of cohorts of COPD participants. Contrary to previous concerns, retrospective analyses also suggest that cardioselective β-blockers may reduce the risk of COPD exacerbations. The proposed study will focus on treating CVD in COPD participants to reduce mortality and morbidity.
The study will be conducted in 23 sites in Australia, New Zealand, India and Sri Lanka. Participants with COPD will be randomised to one of two treatment arms in addition to receiving usual care for their COPD over the study duration of 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants will be eligible for this study if they qualify on all of the following:
- •Have provided written informed consent
- •Have COPD defined by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria
- •Aged 40-85 years
- •FEV1 ≥30% and ≤70% predicted post-bronchodilator
- •FEV1/FVC <0.7 post-bronchodilator
- •Have had a COPD exacerbation in the previous 24 months requiring oral corticosteroid, antibiotics, or both
- •If taking maintenance OCS, dosage is stable and ≤10mg daily for 4 weeks prior to randomisation
- •Resting SBP ≥100mmHg
- •SBP and spirometry criteria must be met after the test dose of bisoprolol of 1.25mg
- •(New Zealand only) A history of cardiovascular disease, including heart failure, ischaemic heart disease, tachyarrhythmias, and hypertension
排除标准
- •Participants will be ineligible for the study if they have any of the following:
- •Concurrent therapy with any other β-blocker
- •Resting HR <60bpm
- •Unstable left HF (i.e. symptomatic and/or necessary change in management in the last 12 weeks, or in clinicians' opinion)
- •Clinically significant pulmonary hypertension, which in the investigator's opinion would be a contraindication for β-blocker therapy
- •Severe end-stage peripheral vascular disease
- •2nd or 3rd degree heart block
- •Currently using or have been prescribed LTOT or resting saturated oxygen level <90% when stable
- •Expected survival is less than 12 months, or in the investigator's opinion, the person has such unstable disease (of any type) that maintaining 12 months' participation would be unlikely
- •Clinical instability since a MACE in the previous 12 weeks
- •Lower respiratory tract infection or AECOPD within the last 8 weeks
- •COPD not clinically stable as determined by the investigator
- •In the clinician's view, have asthma-COPD overlap or co-existent asthma are present; or an improvement in FEV1 ≥400mL post-bronchodilator is observed on two occasions
- •Females of child-bearing age and capability who are pregnant or breastfeeding or those in this group not using adequate birth control
- •Coexistent illness which precludes participation in the study (poorly controlled diabetes, active malignancy)
- •Severe end-stage liver disease defined by INR>1.3 and albumin<30g/L or portal hypertension/ascites
- •High chance in the view of the treating physician that the potential participant will not adhere to study requirements
研究组 & 干预措施
Bisoprolol
1.25, 2.5 or 5mg of bisoprolol daily
干预措施: Bisoprolol (Drug)
Placebo
1.25, 2.5 or 5mg of matched placebo daily
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
All-cause mortality
时间窗: Baseline to 24 months
Composite outcome of the following that will be analysed using a win-ratio apprach according to clinical importance
Hospitalisation for COPD exacerbation
时间窗: Baseline to 24 months
Hospitalisation for primary cardiac cause (ischaemia, arrhythmia, heart failure or ischaemic stroke)
时间窗: Baseline to 24 months
Moderate COPD exacerbation - not hospitalised by treated with oral corticosteroids/antibiotics or both
时间窗: Baseline to 24 months
Cardiac Hospitalisation for cardiac cause other than ischemia, arrythmia or heart failure
时间窗: Baseline to 24 months
Decrease in FEV1 or greatest FEV1% drop - largest decrease in FEV1 from post-bronchodiliator spirometry at baseline
时间窗: Baseline to 24 months
Higher SGRQ score (clinically important change >= 4)
时间窗: Baseline to 12 and 24 months
Respiratory hospitalisation for a respiratory cause other than COPD exacerbation
时间窗: Baseline to 24 months
Mild COPD exacerbation - treated with increased inhalers/inhaler technique/addition of theophylline
时间窗: Baseline to 24 months
Higher CAT score (clinically important change >= 2)
时间窗: Baseline to 12 and 24 months
次要结局
- Severe (hospital admission) COPD exacerbation rate (annualised)(Baseline to 24 months)
- Quality of life assessed by St George's Respiratory Questionnaire (SGRQ)(Baseline to 24 months)
- Time to first moderate-severe COPD Exacerbation(Baseline to 24 months)
- Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE(Baseline to 24 months)
- EuroQoL Group 5-5 Dimension self-report questionnaire (EQ-5D-5L) to assess health state utilities(Baseline to 24 months)
- Clinic spirometry: % predicted post-bronchodilator(Baseline to 24 months)
- 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.(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)
- Hospital admissions for all respiratory causes(Baseline to 24 months)
- Hospital admissions for all cardiac causes(Baseline to 24 months)
- Time to a composite outcome (includes any) of: all-case mortality; hospitalisation for COPD exacerbation, hospitalisation for primary cardiac cause (arrytmmia, ischaemia or heart failure) or MACE(Baseline to 24 months)
- COPD exacerbation rate (annualised)(Baseline to 24 months)