Status: Finalised
First registered on:
14/07/2015
Last updated on:
21/03/2019
1. Study identification
EU PAS Register NumberEUPAS10254
Official titleThromboembolic Risk in Patients with Chronic Kidney Disease Treated receiving Epoetin zeta or other Erythropoietin Stimulating Agents – the BIPS study
Study title acronym
Study typeObservational study
Brief description of the studyErythropoietin belongs to the group of erythropoiesis-stimulating agents (ESAs) that stimulate the production of red blood cells from the bone marrow. Erythropoietin-containing medicines are used to treat anaemia in patients with cancer who are receiving chemotherapy and in patients with chronic kidney disease (CKD). Currently several medicinal products containing erythropoietin are approved in the European Union including biosimilar products. One of those is epoetin zeta which was licensed 2007 and is marketed in Germany as Silapo®. Several studies showed an increased risk for thromboembolic events associated with ESA use; if ESAs differ with respect to their thromboembolic properties is unknown. To examine the risk of thromboembolic events in patients with CKD treated with ESAs, a retrospective cohort study based on data from the German Pharmacoepidemiological Research database will be conducted for the years 2007 to 2011. The study will compare the risk of thromboembolic events such as myocardial infarction, deep vein thrombosis or pulmonary embolism in patients treated with Epoetin zeta as compared with patients receiving epoetin alpha or other ESAs.
Was this study requested by a regulator?Yes: Germany
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
Centre to which the investigator belongsBIPS GmbH
Department/Research groupClinical Epidemiology
Organisation/affiliationLeibniz Inst. for Prevention Research and Epidem.
Details of (Primary) lead investigator
Title Dr
Last name Schink
First name Tania
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
Germany
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed28/07/201128/07/2011
Start date of data collection01/01/200701/01/2007
Start date of data analysis
Date of interim report, if expected
Date of final study report31/03/201710/03/2017
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesSTADA Arzneimittel AG100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Schink
First name Tania
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode28359
CountryGermany
Phone number (incl. country code)49-421-21856860
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Schink
First name Tania
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode
CountryGermany
Phone number (incl. country code)004942121856865
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)B03XA01 (erythropoietin)
Substance class (ATC Code)B03XA02 (darbepoetin alfa)
Substance class (ATC Code)B03XA03 (methoxy polyethylene glycol-epoetin beta)
7. Medical conditions to be studied
Medical condition(s)Yes
Chronic kidney disease
8. Population under study
Age
Preterm newborns
Term newborns (0-27 days)
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Adolescents (12 - 17 years)
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 subjects5200
Additional information
ca. 5,200 patients in the study cohort
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Administrative database, e.g. claims database
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?
The primary objective of this study is to compare the incidence of thromboembolic events in patients with renal anaemia treated with epoetin zeta and patients with renal anaemia treated with epoetin alpha.
Are there primary outcomes?Yes
The main study endpoint is the composite endpoint of the three thromboembolic events:
• Acute myocardial infarction
• Deep vein thrombosis and/or pulmonary embolism
• Cerebrovascular event i.e. cerebrovascular accident, cerebral infarction, transient ischaemic attack or cerebral haemorrhage.
Are there secondary outcomes?Yes
These three events will be analysed separately as secondary outcomes.
13. Study design
What is the design of the study?
Nested case-control study
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
The risk of thromboembolic events in CKD patients treated with epoetin zeta will be compared to the risk of thromboembolic events in CKD patients treated with epoetin alpha or other epoetins in a case-control analysis. Epoetin users will be identified based on drug prescriptions. Risk assessment in all groups of patients during the study period will be based on hospital or outpatient diagnoses. Information on sex, year of birth, SHI, co-morbidity, and co-medication will be gathered for the study period and for the year before cohort entry. Cases will be defined as current users if they are exposed to any ESA on the index day, as recent users if ESA exposure ends 1-30 days before the index day, and as past users if ESA exposure ends > 30 days before the index day.
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
