Gertz 2010

Methods	Study design: RCT Study duration: NS
Participants	Setting: 50 centres Countries: 10 (Bosnia, Bulgaria, Croatia, Hungary, Israel, Poland, Romania, Russia, Serbia, Turkey) Stage of CKD: eGFR below 60 mL/min/1.73 m² Mean age ± SD (years): epoetin beta (61.7 ± 15.7), biosimilar epoetin theta (64.1 ± 13.1) Sex (M/F): epoetin beta (59/36), female (92/101) Other characteristics: Hb 9.5 to 12.0 g/dL; adequate iron stores Exclusion criteria: conditions known to cause anaemia; but not related to CKD (e.g. active bleeding); RBC transfusion within the last 3 months; female patients of childbearing potential; uncontrolled severe hypertension; congestive heart failure (New York Heart Association class III or IV); severe metabolic acidosis; current systemic infection or inflammatory disease; current malignant disease; resistance to epoetin (more than 300 IU/kg body weight/wk); known hypersensitivity to epoetin or excipients of the formulation; known presence of antibodies to epoetin
Interventions	Treatment group Epoetin beta SC aiming for Hb level 9.5 to 12.0 g/dL for 6 months Control group Biosimilar epoetin theta SC aiming for Hb level 9.5 to 12.0 g/dL for 6 months Iron supplementation As required
Outcomes	Primary study outcome Hb level change from baseline to end of treatment Outcomes for meta‐analysis All‐cause mortality Cardiovascular events Hypertension
Notes	Funding: BioGeneriX AG Trials registration: EudraCT No. 2005‐000142‐37 Contact with study authors: contacted (no reply or data received)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Unclear
Allocation concealment (selection bias)	Low risk	Interactive voice‐response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Drug administered by third party who was aware of treatment assignment
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	20/95 lost to follow‐up in epoetin beta arm (21%) and 34/193 lost to follow‐up in biosimilar epoetin theta arm (18%). As this was > 10%, this was judged to be high risk
Selective reporting (reporting bias)	Low risk	Data for major cardiovascular events available
Other bias	Low risk	Sponsor on authorship and involved in statistical analysis