Klinkmann 1992

Methods	Study design: RCT Study duration: NS
Participants	Setting: 16 dialysis centres Country: Germany, Czech Republic, Russia, Latvia, Romania, Bulgaria, Macedonia Stage of CKD: HD Number: epoetin beta (181), no treatment (181) Mean age ± SD (years): NS Sex (M/F): 162/200 Other characteristics: mean packed volume ≤ vol% or requiring at least one blood transfusion in the 4 weeks before randomisation Exclusion criteria: acute decompensated ESKD; septicaemia; acute infections; iron deficiency; therapy involving cytostatic agents; hormone preparations (except thyroid therapy, contraceptives, and insulin) or immunosuppressants; malignant growth; acute liver disease; uncontrolled hypertension; epilepsy; pregnancy; folic acid, or vitamin B12 deficiency; haemolytic‐uraemic syndrome; thrombocytosis(> 500,000 mm³) and participation within the last 4 weeks
Interventions	Treatment group Epoetin beta SC starting at 20 U/kg body weight 3 times/wk until HCT 30% to 35% reached for 12 months Control group No treatment Iron supplementation NS
Outcomes	Primary trial outcome Safety Outcomes extracted for meta‐analysis All‐cause mortality Major adverse cardiovascular events Hypertension Dialysis vascular access thrombosis
Notes	Funding: Boehringer Mannheim GmbH. Trials registration: not applicable Contact with authors: not contacted
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	High risk	Open label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	34/181 (19%) lost in epoetin alfa group and 39/181 (21.5%) lost in control group. As this is > 10% this was judged to be high risk
Selective reporting (reporting bias)	Low risk	Major cardiovascular event data available
Other bias	High risk	Industrial sponsor on authorship