1. Study identification
EU PAS Register NumberEUPAS5711
Official titleObservational, non-interventional, multicenter study of adverse events in hemodialysis patients receiving ESA (erythropoiesis-stimulating agents) originators or biosimilars
Study title acronymESAVIEW -View on erythropoiesis-stimulating agents
Study typeObservational study
Brief description of the studyBackground: Erythropoietin is a growth factor that primarily stimulates red cell production and it is produced by the kidneys. When there is a chronic renal failure, the erythropoietin’s production is not sufficient for the growth of red blood cells and these patients develop anemia. ESAs are administered to anaemic patients. Epoetin alfa has been the first representative of ESA. The patient of epoetin alfa was expired in 2004 and in this year EMA approved two biosimilars of epoetina alfa. These drugs are produced by recombinant DNA technology and the major preoccupation is the immunogenicity. For the complexity of the production process it is necessary a pharmacovigilance’s activity. The study estimates the incidence of adverse event (AE) that happen in patients making hemodialysis and taking ESA. Objectives: The main objective is the safety profile of ESAs: originators and biosimilars. The secondary objectives are the effectiveness and the cost-effectiveness of ESA (originators and biosimilars). Methods: It’s an observational study and the prescription drugs in question are part of the normal clinical practice. The originators observed are Eprex®, Neorecormon®, Aranesp® and Mircera®. The biosimilars are Binocrit® and Retacrit®. The study is conducted in these regions: Veneto (center coordinator), Calabria, Liguria, Molise and Sardinia. Each region has one or more monitors. Inclusion criteria are: 1) patients who do the dialysis at least two times a week; 2) patients receiving ESAs; 3) patients older than 18 years. Esclusion criteria are: patients who are not able to read and sign the informed consent. Criteria for the exit during the study are: 1) patients who are transplanted; 2) patients who switch to peritoneal dialysis. Monitors have to register on a electronic Case Report Form: patient data, drug therapy and specific laboratory tests and adverse event. Results: we are working on and results will be published as soon as available.
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 groupPharmacology Unit - Veneto Pharmacovigilance Centre
Organisation/affiliationUniversity Hospital Verona
Details of (Primary) lead investigator
Title Professor
Last name Ugo
First name Moretti
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?24
15 dialysis centre, Veneto Region
3 dialysis centre, Sardinia Region
4 dialysis centre, Molise Region
1 dialysis centre, Liguria Region
1 dialysis centre, Calabria Region
Countries in which this study is being conducted
National study
Italy
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/01/201101/01/2011
Start date of data collection01/09/201301/10/2013
Start date of data analysis01/01/201506/10/2017
Date of interim report, if expected
Date of final study report31/12/201520/07/2018
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government bodyAIFA_ Italian Medines Agency100
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Conforti
First name Anita
Address line 1Pharmacology Unit
Address line 2Policlinico G.B. Rossi
Address line 3P.zzale L.A. Scuro, 10
CityVerona
Postcode37134
CountryItaly
Phone number (incl. country code)390458124245
Alternative phone number390458027602
Fax number (incl. country code)390458124876
Public Enquiries
Title Professor
Last name Conforti
First name Anita
Address line 1Pharmacology Unit
Address line 2Policlinico G.B. Rossi
Address line 3P.zzale L.A. Scuro, 10
CityVerona
Postcode37134
CountryItaly
Phone number (incl. country code)390458124245
Alternative phone number390458027602
Fax number (incl. country code)390458124876
6. Study drug(s) information
Substance class (ATC Code)B03XA01 (erythropoietin)
Substance class (ATC Code)B03XA02 (darbepoetin alfa)
7. Medical conditions to be studied
Medical condition(s)Yes
Dialysis
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 subjects1600
Additional information
The study estimates the incidence of adverse event (AE) that happen in patients making hemodialysis and taking ESA. We estimate to enroll about 1600 patients
10. Source of data
Is this study being carried out with an established data source?No
Sources of data
Prospective patient-based data collection
11. Scope of the study
What is the scope of the study?
Risk assessment
Drug utilisation study
Effectiveness evaluation
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
The main objective is the safety profile of ESAs: originators and biosimilars. The secondary objectives are the effectiveness and the cost-effectiveness of ESA (originators and biosimilars).
Are there primary outcomes?Yes
Adverse events to ESAs (originators vs biosimilars)
Are there secondary outcomes?Yes
Utilization and effectiveness of ESAs (originators vs biosimilars)
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
One year of follow -up for each patient
15. Data analysis plan
Please provide a brief summary of the analysis method
For each variable and for each endpoint a statistic description with a confidence intervals at 95% will be produced. The primary endpoint will be synthesized by specific indicators such as the cumulative incidence in each cohort, the incidence rate and the incidence patients. The stratification will be based on appropriate indicators such as: the time of exposure to erythropoietin prior to the start of the study, the time passed since the first dialysis and the number of changes of erythropoietin. For each exposure the incidence rate will also be calculated. Categorical variables will be analyzed using univariate (the Chi square test and Fisher's exact test) or multivariate analysis (logistic regression) . Continuous variables will be analyzed using parametric (eg, t-tests, ANOVA) or non-parametric (eg, Mann-Witney test) analysis. The variables "time to failure" will be analyzed by Kaplan Meier method or Cox regression. All tests will be carried out in two tails.