Preventing Adverse Cardiac Events in COPD
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|ClinicalTrials.gov Identifier: NCT03917914|
Recruitment Status : Recruiting
First Posted : April 17, 2019
Last Update Posted : July 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease Cardiovascular Diseases||Drug: Bisoprolol Drug: Placebo Oral Tablet||Phase 3|
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 approximately 20 sites in Australia and New Zealand, and possibly 1-2 international sites. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1164 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Preventing Adverse Cardiac Events in Chronic Obstructive Pulmonary Disease|
|Actual Study Start Date :||June 30, 2020|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Active Comparator: Bisoprolol
1.25, 2.5 or 5mg of bisoprolol daily
As in arm description
Placebo Comparator: Placebo
1.25, 2.5 or 5mg of matched placebo daily
Drug: Placebo Oral Tablet
As in arm description
- All-cause mortality [ Time Frame: Baseline to 24 months ]
- Hospitalisation for COPD exacerbation [ Time Frame: Baseline to 24 months ]
- Hospitalisation for primary cardiac cause (ischaemia, arrhythmia or heart failure) [ Time Frame: Baseline to 24 months ]
- Major Adverse Cardiovascular Event (MACE) [ Time Frame: Baseline to 24 months ]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.
- COPD exacerbation rate (annualised) [ Time Frame: Baseline to 24 months ]
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 [ Time Frame: Baseline to 24 months ]
- Severe (hospital admission) COPD exacerbation rate (annualised) [ Time Frame: Baseline to 24 months ]
- Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE [ Time Frame: Baseline to 24 months ]
- Quality of life assessed by St George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline to 24 months ]
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 [ Time Frame: Baseline to 24 months ]
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 [ Time Frame: Baseline to 24 months ]
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) [ Time Frame: Baseline to 24 months ]
- Clinic spirometry: post-bronchodilator FEV1 (Forced Expiratory Volume) (L) [ Time Frame: Baseline to 24 months ]
- Clinic spirometry: % predicted post-bronchodilator [ Time Frame: Baseline to 24 months ]
- Hospital admissions for all respiratory causes [ Time Frame: Baseline to 24 months ]
- Hospital admissions for all cardiac causes [ Time Frame: Baseline to 24 months ]All cardiac causes includes ischaemia, arrhythmia, heart failure, acute arrhythmia, non-ST-elevation myocardial infarction, urgent revascularisation (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. [ Time Frame: Baseline to 24 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03917914
|Contact: Dr Allison Humphries||+61 2 8052 email@example.com|
|Contact: Grace Balickifirstname.lastname@example.org|
|Principal Investigator:||Prof Christine Jenkins||The George Institute|