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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03917914
Ethics application status
Date submitted
10/04/2019
Date registered
17/04/2019
Date last updated
18/01/2024

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, heart failure or ischaemic stroke)
Timepoint [3] 0 0
Baseline to 24 months
Primary outcome [4] 0 0
Moderate COPD exacerbation - not hospitalised by treated with oral corticosteroids/antibiotics or both
Timepoint [4] 0 0
Baseline to 24 months
Primary outcome [5] 0 0
Cardiac Hospitalisation for cardiac cause other than ischemia, arrythmia or heart failure
Timepoint [5] 0 0
Baseline to 24 months
Primary outcome [6] 0 0
Respiratory hospitalisation for a respiratory cause other than COPD exacerbation
Timepoint [6] 0 0
Baseline to 24 months
Primary outcome [7] 0 0
Decrease in FEV1 or greatest FEV1% drop - largest decrease in FEV1 from post-bronchodiliator spirometry at baseline
Timepoint [7] 0 0
Baseline to 24 months
Primary outcome [8] 0 0
Mild COPD exacerbation - treated with increased inhalers/inhaler technique/addition of theophylline
Timepoint [8] 0 0
Baseline to 24 months
Primary outcome [9] 0 0
Higher SGRQ score (clinically important change >= 4)
Timepoint [9] 0 0
Baseline to 12 and 24 months
Primary outcome [10] 0 0
Higher CAT score (clinically important change >= 2)
Timepoint [10] 0 0
Baseline to 12 and 24 months
Secondary outcome [1] 0 0
Time to first moderate-severe COPD Exacerbation
Timepoint [1] 0 0
Baseline to 24 months
Secondary outcome [2] 0 0
Severe (hospital admission) COPD exacerbation rate (annualised)
Timepoint [2] 0 0
Baseline to 24 months
Secondary outcome [3] 0 0
Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE
Timepoint [3] 0 0
Baseline to 24 months
Secondary outcome [4] 0 0
Quality of life assessed by St George's Respiratory Questionnaire (SGRQ)
Timepoint [4] 0 0
Baseline to 24 months
Secondary outcome [5] 0 0
EuroQoL Group 5-5 Dimension self-report questionnaire (EQ-5D-5L) to assess health state utilities
Timepoint [5] 0 0
Baseline to 24 months
Secondary outcome [6] 0 0
Healthcare utilisation costs and Quality Adjusted Life Years (QALYs) evaluation of the treatment intervention
Timepoint [6] 0 0
Baseline to 24 months
Secondary outcome [7] 0 0
Health status assessed by COPD Assessment Test (CAT)
Timepoint [7] 0 0
Baseline to 24 months
Secondary outcome [8] 0 0
Clinic spirometry: post-bronchodilator FEV1 (Forced Expiratory Volume) (L)
Timepoint [8] 0 0
Baseline to 24 months
Secondary outcome [9] 0 0
Clinic spirometry: % predicted post-bronchodilator
Timepoint [9] 0 0
Baseline to 24 months
Secondary outcome [10] 0 0
Hospital admissions for all respiratory causes
Timepoint [10] 0 0
Baseline to 24 months
Secondary outcome [11] 0 0
Hospital admissions for all cardiac causes
Timepoint [11] 0 0
Baseline to 24 months
Secondary outcome [12] 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 [12] 0 0
Baseline to 24 months
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline to 24 months
Secondary outcome [14] 0 0
COPD exacerbation rate (annualised)
Timepoint [14] 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 40-85 years
4. FEV1 =30% and =70% predicted post-bronchodilator
5. FEV1/FVC <0.7 post-bronchodilator
6. Have had a COPD exacerbation in the previous 24 months requiring oral corticosteroid, antibiotics, or both
7. If taking maintenance OCS, dosage is stable and =10mg daily for 4 weeks prior to randomisation
8. Resting SBP =100mmHg
9. SBP and spirometry criteria must be met after the test dose of bisoprolol of 1.25mg
10. (New Zealand only) A history of cardiovascular disease, including heart failure, ischaemic heart disease, tachyarrhythmias, and hypertension
Minimum age
40 Years
Maximum age
85 Years
Sex
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. Concurrent therapy with any other ß-blocker
2. Resting HR <60bpm
3. Unstable left HF (i.e. symptomatic and/or necessary change in management in the last 12 weeks, or in clinicians' opinion)
4. Clinically significant pulmonary hypertension, which in the investigator's opinion would be a contraindication for ß-blocker therapy
5. Severe end-stage peripheral vascular disease
6. 2nd or 3rd degree heart block
7. Currently using or have been prescribed LTOT or resting saturated oxygen level <90% when stable
8. 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
9. Clinical instability since a MACE in the previous 12 weeks
10. Lower respiratory tract infection or AECOPD within the last 8 weeks
11. COPD not clinically stable as determined by the investigator
12. 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
13. Females of child-bearing age and capability who are pregnant or breastfeeding or those in this group not using adequate birth control
14. Coexistent illness which precludes participation in the study (poorly controlled diabetes, active malignancy)
15. Severe end-stage liver disease defined by INR>1.3 and albumin<30g/L or portal hypertension/ascites
16. 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
Accrual to date
Final
280
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
TrialsWest Pty Ltd - Perth
Recruitment hospital [11] 0 0
Institute for Respiratory Health - 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/study/NCT03917914
Trial related presentations / publications
Martin A, Hancox RJ, Chang CL, Beasley R, Wrobel J, McDonald V, Dobler CC, Yang IA, Farah CS, Cochrane B, Hillis GS, Scowcroft CP, Aggarwal A, Di Tanna GL, Balicki G, Galgey S, Jenkins C. Preventing adverse cardiac events (PACE) in chronic obstructive pulmonary disease (COPD): study protocol for a double-blind, placebo controlled, randomised controlled trial of bisoprolol in COPD. BMJ Open. 2021 Aug 27;11(8):e053446. doi: 10.1136/bmjopen-2021-053446.
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

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