Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000839404
Ethics application status
Approved
Date submitted
21/06/2016
Date registered
28/06/2016
Date last updated
31/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Beta-blockers in chronic obstructive pulmonary disease (COPD): Feasibility study
Scientific title
Beta-blockers in COPD: Feasibility of an RCT in stable patients
Secondary ID [1] 289511 0
nil
Universal Trial Number (UTN)
U1111-1182-7193
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COPD 299215 0
Condition category
Condition code
Respiratory 299223 299223 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A feasibility study to assess whether cardio-selective beta-blockers can be started in patients with stable COPD. If patients can tolerate the drug, this will inform future randomised, placebo-controlled trial.
Oral bisoprolol will be started at a dose of 1.25mg daily, increased to 2.5mg daily after 2 weeks and to a target dose of 5mg daily after a further 4 weeks if tolerated. This dose will be maintained for a further 6 weeks.
Compliance will not be objectively monitored
Intervention code [1] 295102 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298700 0
Ability to recruit eligible patients - percent of eligible patients screened who are started on the beta-blocker
Timepoint [1] 298700 0
one year
Primary outcome [2] 298701 0
Proportion of patients who tolerate cardio-selective beta-blockers, judged by the proportion of participants who remain on the beta-blockers at the end of the study (self-report).
Timepoint [2] 298701 0
3 months after starting drug
Secondary outcome [1] 325005 0
Proportion of patients who reach the target dose of 5mg bisoprolol once daily. Assessed by the number of participants who are dispensed the drug and report taking it.
Timepoint [1] 325005 0
3 months after starting drug
Secondary outcome [2] 325006 0
Proportion of patients experiencing beta-blocker related adverse events and description of these adverse events.
All adverse events will be noted: these events will be detected by self-report, clinical notes, third-party reports (e.g. other doctors or coroner) and/or clinical observations at follow-up,
Pulse, blood pressure, spirometry, and ECGs will be done at each follow-up visit to record the cardiovascular and airway effects of the drug.
Timepoint [2] 325006 0
3 months after starting drug

Eligibility
Key inclusion criteria
Clinical diagnosis of COPD
FEV1/FVC ratio <70% on spirometery
History of COPD exacerbation in previous 2 years
Currently clinically stable
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Clinical diagnosis of asthma
Contraindication to beta-blockers
Active cancer or terminal illness
Pregnant or breastfeeding
Acute coronary syndrome

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
None
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive analysis of the proportions of patients able to be recruited, the number who tolerate the beta-blocker drug, and the number experiencing adverse events.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/08/2016
Actual
29/11/2016
Date of last participant enrolment
Anticipated
30/06/2017
Actual
27/11/2017
Date of last data collection
Anticipated
30/03/2018
Actual
Sample size
Target
48
Accrual to date
Final
37
Recruitment outside Australia
Country [1] 7980 0
New Zealand
State/province [1] 7980 0

Funding & Sponsors
Funding source category [1] 293885 0
Government body
Name [1] 293885 0
Health Research Council
Country [1] 293885 0
New Zealand
Primary sponsor type
Individual
Name
Robert Hancox
Address
Dunedin School of Medicine,
University of Otago,
PO Box 913
Dunedin.
New Zealand


9054
Country
New Zealand
Secondary sponsor category [1] 292719 0
Individual
Name [1] 292719 0
Catherina Chang
Address [1] 292719 0
Department of Respiratory Medicine
Waikato Hospital
Pembroke St
Hamilton

3240
Country [1] 292719 0
New Zealand
Other collaborator category [1] 279042 0
Individual
Name [1] 279042 0
Lutz Beckert
Address [1] 279042 0
Department of Medicine
University of Otago,
PO Box 4345
Christchurch


8140
Country [1] 279042 0
New Zealand
Other collaborator category [2] 279043 0
Individual
Name [2] 279043 0
Richard Beasley
Address [2] 279043 0
Medical Research Institute of New Zealand
Level 7, CSB building,
Riddiford St,
Private Bag 7902
Wellington

6021
Country [2] 279043 0
New Zealand
Other collaborator category [3] 279044 0
Individual
Name [3] 279044 0
Conroy Wong
Address [3] 279044 0
Middlemore Hospital,
100 Hospital Road,
Papatoetoe,
Auckland


2025
Country [3] 279044 0
New Zealand
Other collaborator category [4] 279047 0
Individual
Name [4] 279047 0
Catherina Chang
Address [4] 279047 0
Department of Respiratory Medicine
Waikato Hospital
Pembroke St
Hamilton


3240
Country [4] 279047 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295302 0
Southern Health & Disability Ethics Committee
Ethics committee address [1] 295302 0
Ethics committee country [1] 295302 0
New Zealand
Date submitted for ethics approval [1] 295302 0
08/06/2016
Approval date [1] 295302 0
03/08/2016
Ethics approval number [1] 295302 0

Summary
Brief summary
Rationale for Research
Cardiac diseases are a major cause of death in patients with chronic obstructive pulmonary disease (COPD). Patients with exacerbations of COPD are at risk of cardiac complications and these may be the most important determinant of survival in these patients. In addition, both of the commonly used classes of bronchodilators may increase cardiovascular risk and are used in high doses during exacerbations. Protecting patients with exacerbations of COPD from cardiac complications may have a greater impact on mortality than existing respiratory treatments. Beta-blockers are a valuable class of drug for protecting the heart and retrospective studies suggest that beta-blockers could reduce mortality in COPD. However patients with COPD have been excluded from prospective clinical trials of beta-blockers and continue to be denied treatment with them because of concerns that they may worsen airways disease. Several observational studies suggest that beta-blockers are safe and that they reduce mortality in patients with COPD. However, these studies have been prone to bias and confounding.
We recently completed a study to assess the feasibility of conducting an RCT of beta-blockers in patients in hospital with exacerbations of COPD. It became clear that we could not do an RCT in this setting. Our aim now to assess whether it is feasible to do an RCT in stable patients with a history of COPD exacerbations
Aims
Before we conduct a randomised placebo-controlled trial of the cardio-selective beta-blocker metoprolol in patients with stable COPD, we are doing this feasibility study to explore two practical aspects of the proposed study:
1. Can beta-blockers be safely commenced in patients with a history of exacerbations of COPD? Although some patients with COPD take regular beta-blockers, it is not known what proportion of patients will be able to tolerate them. We aim to recruit 48 patients (12 in 4 centres) to establish whether cardio-selective beta-blockers can be commenced in patients with a history of exacerbations and what proportion of them tolerate the drug.
2. What proportion of patients with a history of exacerbations of COPD will be eligible for recruitment, how many consent to take part, how many will be excluded for reasons such as contra-indications to beta-blocker (e.g. childhood asthma, peripheral vascular disease), pre-existing beta-blocker treatment, or have other medical conditions such as advanced malignancy and would be unlikely to benefit from beta-blockers? This information will be important for planning recruitment to the main study.
Protocol
This feasibility study will recruit patents with COPD and start them on a low dose of metoprolol increasing to a target dose of 95mg daily over 6 weeks. The study will finish after 3 months - after 6 weeks on the highest dose.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 66818 0
A/Prof Bob Hancox
Address 66818 0
Dept of Preventive & Social Medicine
Dunedin School of Medicine
PO Box 913
University of Otago


9054
Country 66818 0
New Zealand
Phone 66818 0
+6434798512
Fax 66818 0
Email 66818 0
[email protected]
Contact person for public queries
Name 66819 0
A/Prof Bob Hancox
Address 66819 0
Dept of Preventive & Social Medicine
Dunedin School of Medicine
PO Box 913
University of Otago


9054
Country 66819 0
New Zealand
Phone 66819 0
+6434798512
Fax 66819 0
Email 66819 0
[email protected]
Contact person for scientific queries
Name 66820 0
A/Prof Bob Hancox
Address 66820 0
Dept of Preventive & Social Medicine
Dunedin School of Medicine
PO Box 913
University of Otago



9054
Country 66820 0
New Zealand
Phone 66820 0
+6434798512
Fax 66820 0
Email 66820 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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