Krivoshiev 2010

Methods	Study design: RCT Study duration: NS
Participants	Setting: 42 dialysis centres Countries: Bulgaria, Germany, Poland, Romania, Serbia Stage of CKD: HD Number: epoetin alfa (230), biosimilar epoetin zeta (232) Mean age ± SD (years): epoetin alfa (55.2 ± 12.58), biosimilar epoetin zeta (55.6 ± 12.47) Sex (M/F): epoetin alfa (134/96), biosimilar epoetin zeta (138/94) Other characteristics: anaemia treated with epoetin Exclusion criteria: severe diseases within the last 6 months prior to main study phase (e.g. myocardial infarction, stroke, unstable angina, decompensated congestive heart failure, or thromboembolic events); conditions known to also cause anaemia (e.g. acute bleeding and/or recently documented haemorrhage, documented bleeding disorders, haemolysis, clinically manifested deficiency of folic acid and/or vitamin B12, or bone marrow fibrosis); epilepsy; malignant tumours; uncontrolled hypertension; CRP > 10 mg/dL; detectable neutralising anti‐erythropoietin antibodies; hypersensitivity to epoetin; clinically relevant changes of dialysis regimen and/or dialyser during the trial; relative or absolute iron deficiency at the end of run‐in period
Interventions	Treatment group Epoetin alfa SC targeting Hb levels 10.0 to 12.0 g/dL for 6 months Control group Biosimilar epoetin zeta SC targeting Hb levels 10.0 to 12.0 g/dL for 6 months Iron supplementation NS
Outcomes	Primary trial outcome Mean weekly epoetin dosage/kg body weight Mean Hb level Outcomes extracted for meta‐analysis All‐cause mortality Transfusion Myocardial infarction Stroke Hypertension
Notes	Funding: STADA R&D GmbH Trials registration: NS Contact with authors: contacted (no reply or data received)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	65/230 lost to follow‐up in epoetin alfa arm (28%) and 78/232 lost to follow‐up in biosimilar epoetin arm (34%). As this was > 10%, this was adjudicated as high risk
Selective reporting (reporting bias)	Low risk	Data for cardiovascular events available
Other bias	High risk	Sponsor on authorship