Status: Planned
First registered on:
25/05/2020
Last updated on:
25/05/2020
1. Study identification
EU PAS Register NumberEUPAS35439
Official titleComparative safety of extrafine beclometasone fixed dose combinations (FDC) and fluticasone FDC in COPD
Study title acronym
Study typeObservational study
Brief description of the studyA historical cohort study, comparing time to pneumonia events in patients with COPD who initiated a fixed dose combination containing beclometasone (Fostair® or Trimbow®) with
• Patients initiating a fixed dose combination containing fluticasone
• Patients initiating a long-acting bronchodilator
The primary outcome is time until a pneumonia event. The secondary outcome is time until a respiratory infection.
The following exploratory outcomes will be used:
Time until the first pneumonia related hospitalisation: a primary care recorded hospital admission within one month of a physician diagnosed pneumonia
Time to first primary care recorded hospital admission.
The rate of moderate/severe COPD exacerbations and pneumonia events during the entire follow-up period (to be used for a benefit/harm comparison).
A set of confounding handling approaches will be evaluated, and the best one with regard to residual bias will be chosen.
Superiority will be tested in a per protocol analysis comparing the FDC beclomethasone group with the FDC fluticasone reference group, with a superiority margin of 10% (or loge(1.1) on the log scale).
Patients will be censored at the end of data availability (due to leaving the practice, or the last time data were extracted for the practice), 4 weeks after the last prescription containing ICS or 4 weeks after the patient switches to the comparator medication. This four-week period is to ensure we will capture a pneumonia event, even if early symptoms have caused discontinuation of ICS or switching to the other medication.
Non-inferiority will be tested in per protocol analyses comparing the FDC beclometasone group with the LABD reference group, with a non-inferiority margin of a relative difference of 15%. Patients will be censored at the end of data availability (due to leaving the practice, or the last time data were extracted for the practice) or on addition of an ICS.
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 signed01/04/2020
Start date of data collection01/06/2020
Start date of data analysis01/07/2020
Date of interim report, if expected01/09/2020
Date of final study report31/10/2020
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesChiesi pharmaceuticals, Italy100
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)441223967582
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)441223967582
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)R03 (DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES)
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
9. Number of subjects
Estimated total number of subjects60000
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?
Risk assessment
Effectiveness evaluation
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
1. To compare the risk of pneumonia in patients with COPD among new users of ICS FDC with fine-particle fluticasone or extrafine beclometasone, and to assess if this is the same for the different fluticasone salts.
2. To compare the risk of pneumonia in patients with COPD among new users of ICS FDC with extrafine beclomethasone versus long acting bronchodilators
Are there primary outcomes?Yes
time until a pneumonia event
Are there secondary outcomes?Yes
time until a respiratory infection.
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
Patients will be censored at the end of data availability (due to leaving the practice, or the last time data were extracted for the practice), 4 weeks after the last prescription containing ICS or 4 weeks after the patient switches to the comparator medication.
15. Data analysis plan
Please provide a brief summary of the analysis method
1. Superiority will be tested in a per protocol analysis comparing the FDC beclomethasone group with the FDC fluticasone reference group, with a superiority margin of 10% (or loge(1.1) on the log scale).
2. Non-inferiority will be tested in per protocol analyses comparing the FDC beclometasone group with the LABD reference group, with a non-inferiority margin of a relative difference of 15%.
A set of confounding handling approaches will be evaluated, and the best one with regard to residual bias will be chosen.
Time-to-event analysis will be performed to analyse the association between treatment and time to recurrent pneumonia events. Cox regression with the Prentice, Williams and Peterson approach with gap-time will be used. To model the recurrent events, events occurring within 28 days of a previous event are considered part of a single episode. Therefore, the patients will be at risk for a new event starting 28 days after each previous event.
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
