Status: Finalised
First registered on:
30/11/2016
Last updated on:
28/04/2020
1. Study identification
EU PAS Register NumberEUPAS16282
Official titlePost-authorization Safety Study Evaluation of Cardiovascular Events in Users of Mirabegron and Other Treatments for Overactive Bladder
Study title acronym
Study typeObservational study
Brief description of the studyMirabegron is a first in class therapeutic agent, with a mechanism of action distinct from that of antimuscarinic agents indicated for the treatment of overactive bladder (OAB). This post authorization safety study (PASS, or post marketing requirement (PMR) in the US) is designed to generate additional evidence to help evaluate the results observed in the clinical trials. To implement the program, we selected data sources from 5 research centers. The investigators are from RTI Health Solutions, Optum, University of Southern Denmark, Centre for Pharmacoepidemiology at Karolinska Institute, and Comprehensive Health Insights.
The study population will include patients observed in each of the 5 databases, providing a wide array of patient characteristics, drug utilization and medical practice patterns, which will enhance the generalizability of the study findings to the population of mirabegron users in real world practice, beyond clinical trials.
This will be a cohort study comparing the incidence of commonly occurring cardiovascular events among new users of mirabegron and new users of any comparator antimuscarinic medication (as a group) used in the treatment of OAB. To provide a sufficiently large patient population within which to evaluate the safety of mirabegron, the study will be conducted within multiple databases. Each of these populations will be studied according to the same Core protocol, although operational details will vary across sites due to the specifics of the data environments. In addition to data source-specific analyses, estimates obtained from all data sources will be analyzed using a meta-analysis approach.
Overall, the study period includes October 2012 (first observed use of mirabegron in US data) through June 2019 (submission of final study report).
Was this study requested by a regulator?Yes: EMA, United States
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
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
Centre to which the investigator belongsOptum
Department/Research group
Organisation/affiliationOptum
Details of (Primary) lead investigator
Title Dr
Last name Seeger
First name John
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?4
University of Southern Denmark, Odense C. Denmark
Comprehensive Health Insights, Louisville, KY USA
Countries in which this study is being conducted
International study
Denmark
Sweden
United Kingdom
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed10/08/201522/09/2015
Start date of data collection09/01/201706/09/2016
Start date of data analysis20/02/2017
Date of interim report, if expected29/06/2018
Date of final study report28/06/201915/11/2019
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesAstellas Pharma Global Development, Inc.100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Seeger
First name John
Address line 11325 Boylston St.
Address line 210th Floor
Address line 3
CityBoston
Postcode02215
CountryUnited States
Phone number (incl. country code)16175302275
Alternative phone number
Fax number (incl. country code)16175302803
Public Enquiries
Title Dr
Last name Seeger
First name John
Address line 11325 Boylston St.
Address line 210th Floor
Address line 3
CityBoston
Postcode02215
CountryUnited States
Phone number (incl. country code)16175302275
Alternative phone number
Fax number (incl. country code)16175302803
6. Study drug(s) information
Substance class (ATC Code)G04BD12 (mirabegron)
7. Medical conditions to be studied
Medical condition(s)No
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 subjects100000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Data sources not registered with ENCePP
National Death Index, United States
ORD, United States
Humana Databases, United States
Swedish Medical Registry, Sweden
Sources of data
Disease/case registry
Administrative database, e.g. claims database
Routine primary care electronic patient registry
Pharmacy dispensing records
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
Estimate and compare the incidence of CV endpoints within the person-time among users of mirabegron relative to antimuscarinic medication, (a) overall, (b) stratified by naïve user status, (c) restricted to patients 65+ years, (d) restricted to patients at high risk for CV events, (e) by intervals of time since initiation, and (f) by cumulative dose.
Are there primary outcomes?Yes
Acute myocardial infarction, stroke, CV mortality, Major Adverse Cardiovascular Events (MACE) composite outcome, all-cause mortality.
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Drug utilisation study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Follow-up will start on the day after the index prescription and continue until the earliest of: end of the study period, last date of data with validated cardiovascular outcomes within each of the data sources, or disenrollment.
15. Data analysis plan
Please provide a brief summary of the analysis method
Database-specific and meta analyses will be performed. Within each database, mirabegron and antimuscarinic initiators will be 1:1 propensity score matched. Cox proportional hazards regression models will be built for each CV outcome. Models will be developed for: overall study population, stratified by naïve user status, patients 65+ years, patients at high risk for CV events, by intervals of time since initiation, and cumulative dose.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
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
