Status: Ongoing
First registered on:
24/09/2020
Last updated on:
29/10/2020
1. Study identification
EU PAS Register NumberEUPAS35881
Official titleEuropean non-interventional post-authorization safety study related to serious cardiovascular events of myocardial infarction and stroke, and all-cause mortality for romosozumab by the EU-ADR Alliance
Study title acronym
Study typeObservational study
Brief description of the studyThe main objective is to evaluate potential differences in terms of serious cardiovascular adverse events between romosozumab and currently available therapies used in comparable patients in real-world conditions.
Was this study requested by a regulator?Yes: EMA
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 nameUCB Biosciences GmbH
Centre locationMonheim, Germany
Details of (Primary) lead investigator
Title Dr
Last name Personal data of lead investigator will not be disclosed because his/her consent required for disclosure according to applicable data protection laws is not available.
First name Clinical Trial Registries and Results
Is this study being carried out with the collaboration of a research network?
Yes
EU-ADR Alliance
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?7
Countries in which this study is being conducted
International study
Denmark
France
Germany
Italy
Netherlands
Spain
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed30/09/202030/09/2020
Start date of data collection01/10/202001/10/2020
Start date of data analysis30/09/2026
Date of interim report, if expected
Date of final study report31/03/2027
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesUCB Biopharma SRL100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Personal data of lead investigator will not be disclosed because his/her consent required for disclosure according to applicable data protection laws is not available.
First name Clinical Trial Registries and Results
Address line 1Alfred-Nobel-Strasse 10
Address line 2
Address line 3
CityMonheim
Postcode40789
CountryGermany
Phone number (incl. country code)492173481515
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Personal data of lead investigator will not be disclosed because his/her consent required for disclosure according to applicable data protection laws is not available.
First name Clinical Trial Registries and Results
Address line 1Alfred-Nobel-Strasse 10
Address line 2
Address line 3
CityMonheim
Postcode40789
CountryGermany
Phone number (incl. country code)492173481515
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Product NameEvenity
CountryBelgium
Substance INN(s)ROMOSOZUMAB
7. Medical conditions to be studied
Medical condition(s)Yes
Osteoporosis postmenopausal
8. Population under study
Age
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Female
9. Number of subjects
Estimated total number of subjects337200
Additional information
84,300 users of romosozumab.
Up to 252,900 users of other osteoporosis medications of interest (alendronate or alendronic acid (ALN), risedronate, ibandronate, zoledronate, denosumab, and teriparatide).
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
Health Search Database (HSD), Italy
Système National Des Données de Santé (SNDS), France
Sources of data
Administrative database, e.g. claims database
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Risk assessment
Drug utilisation study
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
The overarching objective of this study is to characterize the risk of serious cardiovascular events of myocardial infarction and stroke, and all-cause mortality including cardiovascular death associated with the use of romosozumab, in comparison with other available osteoporosis medications in routine clinical practice in Europe
Are there primary outcomes?Yes
MACE-2 (first occurrence of death [all cause including cardiovascular (CV) death], Myocardial Infarction (MI), or stroke)
Are there secondary outcomes?Yes
- Myocardial Infarction (MI)
- Stroke
- Death due to cardiovascular (CV) causes, ie, MI or stroke
- All-cause mortality
- First occurrence of death (CV causes), MI, or stroke (MACE-1)
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
New users of osteoporosis medications will be followed for a maximum of 24 months from index therapy Initiation.
15. Data analysis plan
Please provide a brief summary of the analysis method
Incidence rates and 95 % confidence intervals for each outcome will be calculated for each study drug cohort using a Poisson model. These will be reported for prespecified intervals of 6, 12, 18, and 24 months after treatment indexes, and will be stratified by several factors including age, prior use of osteoporosis medication, and previous history of cardiovascular event. For comparative safety studies, propensity score matching will be used to match patients using romosozumab to up to 3 users of alendronate. Cox regression models stratified by matched sets will be used to calculate hazard ratios and 95 % CIs for each of the safety endpoints (MI, stroke, MACE-1, and MACE-2) according to drug exposure in the propensity-matched cohorts. The pooled estimates of the incidence rate for the databases will be calculated using the random or fixed effects meta-analysis depending on heterogeneity detected using an I^2 threshold of >40 %.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
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
