Krivoshiev 2008

Methods	Study design: RCT Study duration: 27 December 2004 to 24 January 2006
Participants	Setting: multicentre Countries: Bulgaria, Poland, Serbia, Macedonia Stage of CKD: HD Number: epoetin alfa (304), biosimilar epoetin zeta (305) Mean age ± SD (years): epoetin alfa (53.6 ± 12.7), biosimilar epoetin zeta (52.3 ± 11.9) Sex (M/F): epoetin alfa (177/127), biosimilar epoetin zeta (176/129) Other characteristics: Hb concentration < 9.0 g/dL with or without previous epoetin therapy; optimal iron supplementation Exclusion criteria: conditions known to cause anaemia that were not related to CKD (e.g. documented bleeding disorders, haemolysis, clinically manifested vitamin B12 and/or folic acid deficiency, bone marrow fibrosis, confirmed aluminium intoxication, recent acute bleeding and/or haemorrhage); epilepsy; current malignancy; uncontrolled hypertension; C‑reactive protein level > 10.0 mg/dL; severe disease within the last 6 months (e.g. stroke, unstable angina, myocardial infarction and deep vein thrombosis); pregnancy or lactation; detectable anti‐erythropoietin antibodies with clinical symptoms and history of hypersensitivity to or known lack of response to epoetin. Other exclusion criteria for the treatment period included relative or absolute iron deficiency at the end of the run‐in period; or clinically relevant changes to dialysis during the trial
Interventions	Treatment group Epoetin alfa IV starting at 50 IU/kg 3 times/wk targeting Hb levels 11.0 to 12.0 g/dL for 6 months Control group: Biosimilar epoetin zeta IV starting at 50 IU/kg 3 times/wk targeting Hb levels 11.0 to 12.0 g/dL for 6 months Iron supplementation As required
Outcomes	Primary study outcome Mean weekly dose of epoetin/kg body weight Mean Hb concentration in the last 4 weeks of treatment Outcomes extracted for meta‐analysis All‐cause mortality Transfusion Cardiovascular event
Notes	Funding: NS 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	Randomisation list provided by an independent clinical research organisation
Allocation concealment (selection bias)	Unclear risk	Patients enrolled at each centre were allocated consecutive numbers
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	46/304 lost to follow‐up in epoetin alfa arm (15%) and 32/305 lost to follow‐up in biosimilar epoetin arm (10%). As this was > 10%, this was adjudicated as high risk
Selective reporting (reporting bias)	Low risk	Data for cardiovascular events available
Other bias	Low risk	None apparent