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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03917914




Registration number
NCT03917914
Ethics application status
Date submitted
10/04/2019
Date registered
17/04/2019
Date last updated
30/05/2019

Titles & IDs
Public title
Preventing Adverse Cardiac Events in COPD
Scientific title
Preventing Adverse Cardiac Events in Chronic Obstructive Pulmonary Disease
Secondary ID [1] 0 0
PACE in COPD
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 0 0
Cardiovascular Diseases 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bisoprolol
Treatment: Drugs - Placebo Oral Tablet

Active Comparator: Bisoprolol - 1.25, 2.5 or 5mg of bisoprolol daily

Placebo Comparator: Placebo - 1.25, 2.5 or 5mg of matched placebo daily


Treatment: Drugs: Bisoprolol
As in arm description

Treatment: Drugs: Placebo Oral Tablet
As in arm description

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All-cause mortality
Timepoint [1] 0 0
Baseline to 24 months
Primary outcome [2] 0 0
Hospitalisation for COPD exacerbation
Timepoint [2] 0 0
Baseline to 24 months
Primary outcome [3] 0 0
Hospitalisation for primary cardiac cause (ischaemia, arrhythmia or heart failure)
Timepoint [3] 0 0
Baseline to 24 months
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline to 24 months
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline to 24 months
Secondary outcome [2] 0 0
Time to first moderate-severe COPD Exacerbation
Timepoint [2] 0 0
Baseline to 24 months
Secondary outcome [3] 0 0
Severe (hospital admission) COPD exacerbation rate (annualised)
Timepoint [3] 0 0
Baseline to 24 months
Secondary outcome [4] 0 0
Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE
Timepoint [4] 0 0
Baseline to 24 months
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline to 24 months
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline to 24 months
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline to 24 months
Secondary outcome [8] 0 0
Health status assessed by COPD Assessment Test (CAT)
Timepoint [8] 0 0
Baseline to 24 months
Secondary outcome [9] 0 0
Clinic spirometry: post-bronchodilator FEV1 (Forced Expiratory Volume) (L)
Timepoint [9] 0 0
Baseline to 24 months
Secondary outcome [10] 0 0
Clinic spirometry: % predicted post-bronchodilator
Timepoint [10] 0 0
Baseline to 24 months
Secondary outcome [11] 0 0
Hospital admissions for all respiratory causes
Timepoint [11] 0 0
Baseline to 24 months
Secondary outcome [12] 0 0
Hospital admissions for all cardiac causes - 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).
Timepoint [12] 0 0
Baseline to 24 months
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline to 24 months

Eligibility
Key inclusion criteria
Participants will be eligible for this study if they qualify on all of the following:

1. Have provided written informed consent

2. Have COPD defined by the 2019 Global Initiative for Chronic Obstructive Lung Disease
(GOLD) diagnostic criteria

3. Aged 40 - 90 years

4. FEV1 < 70% predicted after bronchodilator

5. FEV1/FVC (forced vital capacity) <0.7 post bronchodilator

6. Have had a COPD exacerbation in the previous 12 months requiring oral corticosteroid
(OCS), antibiotics, or both

7. If taking maintenance OCS, dosage is stable and < 10 mgs daily for 4 weeks prior to
randomisation

8. Resting Systolic Blood Pressure (SBP)=100mmHg

9. SBP and spirometry criteria must be met after the test dose of bisoprolol of 1.25mg
Minimum age
40 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be ineligible for the study if they have any of the following:

1. Taking any other ß-blocker therapy concurrently

2. Resting Heart Rate < 60 beats per minute (bpm)

3. Unstable left and/or right HF (i.e. symptomatic and/or necessary change in management
in the last 12 weeks, or in clinicians' opinion)

4. Severe end-stage peripheral vascular disease

5. 2nd or 3rd degree heart block

6. Not expected to survive 12 months, or in the investigator's opinion have such unstable
disease (of any type) that maintaining 12 months' participation would be unlikely

7. Not stabilised since a MACE in the previous 12 weeks

8. Lower respiratory tract infection or acute exacerbation of COPD (AECOPD) in the last 4
weeks and not clinically stable

9. In the clinician's view, have asthma-COPD overlap or co-existent asthma

10. Females of child-bearing age and capability who are pregnant or breastfeeding or those
in this group not using adequate birth control

11. Coexistent illness precluding participation in the study (poorly controlled diabetes,
active malignancy)

12. Severe end-stage liver disease defined by International Normalised Ratio (INR) >1.3
and albumin <30g/L or portal hypertension/ascites.

13. High chance in the view of the treating physician that the potential participant will
not adhere to study requirements

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
John Hunter Hospital & Hunter Medical Research Institute - Newcastle
Recruitment hospital [4] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [5] 0 0
Westmead Hospital - Sydney
Recruitment hospital [6] 0 0
Prince Charles Hospital - Brisbane
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [8] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [9] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [10] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2305 - Newcastle
Recruitment postcode(s) [4] 0 0
2139 - Sydney
Recruitment postcode(s) [5] 0 0
2145 - Sydney
Recruitment postcode(s) [6] 0 0
4032 - Brisbane
Recruitment postcode(s) [7] 0 0
4102 - Brisbane
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment postcode(s) [10] 0 0
6000 - Perth
Recruitment postcode(s) [11] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Dunedin
Country [4] 0 0
New Zealand
State/province [4] 0 0
Hamilton
Country [5] 0 0
New Zealand
State/province [5] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03917914
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Prof Christine Jenkins
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dr Allison Humphries
Address 0 0
Country 0 0
Phone 0 0
+61 2 8052 4383
Fax 0 0
Email 0 0
ahumphries@georgeinstitute.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03917914