Status: Ongoing
First registered on:
30/05/2017
Last updated on:
30/05/2017
1. Study identification
EU PAS Register NumberEUPAS19323
Official titleEffectiveness of triple therapy vs. dual bronchodilation in COPD
Study title acronymEffectiveness of triple therapy in COPD
Study typeObservational study
Brief description of the studyMost patients with COPD can be managed using long-acting bronchodilators. Triple therapy – inhaled corticosteroids (ICS) with long-acting muscarinic antagonist and beta agonist (LAMA+LABA) - is the most intensive type of treatment, but it is uncertain whether patients do better on triple therapy [TT] compared to therapy with two bronchodilators only. More evidence is needed so that clinicians can make informed treatment decisions for their patients.
The study aims to examine whether the effectiveness, in terms of reducing COPD-related exacerbations and loss of lung function, of triple therapy is superior to that of dual bronchodilation (LAMA+LABA) in patients with COPD. In addition, the potential heterogeneity of the effectiveness driven by patient’s and therapy characteristics will be studied.
The study uses a historic cohort design, and matches the patients between treatment groups, according to relevant demographic and clinical characteristics using information from anonymous primary care records of COPD patients.
Two designs will be used to study the effectiveness of TT in COPD patients with a history of smoking:
A. Patients who step-up from LAMA+LABA to TT will be compared with patients who remain on LAMA+LABA
B. Patients who step-up from LAMA to TT will be compared with patients who step up to LAMA+LABA
Primary outcomes will be the occurrence of COPD exacerbations (number in first year and time to first event) and the average decline in forced expiratory volume in first second [FEV1] per year during follow-up.
A one year baseline period is used to identify variables for matching, and patients are followed up during an outcome period of at least one year. Exacerbations will be compared using conditional negative binomial regression to estimate the adjusted rate ratios with 95% confidence intervals. Stratified Cox regression will be used to compare the time to first exacerbation and a multilevel regression model to analyse change in FEV1 over time.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research groupObservational and Pragmatic Research Institute Pte Ltd
Organisation/affiliationOPRI Pte Ltd
Details of (Primary) lead investigator
Title Professor
Last name Price
First name David
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/05/201701/05/2017
Start date of data collection15/05/201715/05/2017
Start date of data analysis01/06/2017
Date of interim report, if expected
Date of final study report01/08/2017
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesChiesi100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Price
First name David
Address line 15a Coles Lane
Address line 2Oakington
Address line 3
CityCambridge
PostcodeCB24 3BA
CountryUnited Kingdom
Phone number (incl. country code)44-1223967582
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Professor
Last name Price
First name David
Address line 15a Coles Lane
Address line 2Oakington
Address line 3
CityCambridge
PostcodeCB24 3BA
CountryUnited Kingdom
Phone number (incl. country code)44-1223967582
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Not applicable (disease/epidemiology study)
7. Medical conditions to be studied
Medical condition(s)Yes
Chronic obstructive pulmonary disease
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects25000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Effectiveness evaluation
Primary scope : Effectiveness evaluation
12. Main objective(s)
What is the main objective of the study?
1. To examine whether the effectiveness of triple therapy is superior to that of dual bronchodilation (LAMA+LABA), in terms of reducing COPD-related exacerbations
2. To study the potential heterogeneity of the effectiveness driven by patient’s and therapy characteristics
3. To establish the effectiveness of triple therapy on reducing long-term lung function decline
Are there primary outcomes?Yes
1. COPD exacerbations: number in first year and time to first event
2. Average decline in forced expiratory volume in first second [FEV1] per year
Are there secondary outcomes?Yes
1. Acute courses of oral corticosteroids (number in first year and time to first event)
2. Antibiotic prescriptions following lower respiratory consultation (number in first year and time to first event)
3. Time to first hospitalisation with COPD as primary diagnosis
4. Time to first A&E attendance related to COPD
5. Time to first pneumonia diagnosis
6. mMRC score within 18 months
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
historical follow-up study (data already collected)
15. Data analysis plan
Please provide a brief summary of the analysis method
Patients will be matched between treatment groups, according to relevant demographic and clinical characteristics.
Conditional negative binomial regression will be performed to estimate adjusted Rate Ratios (RR) with 95% confidence intervals (CI) for the effect of treatment on outcomes that involve counted numbers of events over fixed time periods.
An intention-to-treat time-to-event analysis will be performed to analyse the association between treatment and time to the first outcome event during follow-up after ID with right censoring at the time of death or loss to follow-up.
Stratified Cox regression will be performed with time to the first event as the outcome variable to estimate Hazard Ratios (HR) with 95% CI of the treatment effect.
Effect modification by patient and therapy characteristics will be studied by including interaction terms into the model.
For objective 3, the change in FEV1 over time will be analysed using a multilevel model for change.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Available when the study ends
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
