Lillevang 1990.

Study characteristics
Methods	Study design Parallel RCT Study dates Duration of follow‐up: 8 weeks Time frame: not reported
Participants	Study characteristics Setting: not reported Country: Denmark Inclusion criteria: HD for at least 3 months and Hb < 5.6 mmol/L (the average value based on at least 3 measurements within the last 3 weeks before inclusion in the study) Exclusion criteria: < 18 years; pregnancy or nursing women; serum ferritin < 150 μg/L; malignant disease; BP > 160/90 mm Hg (the average value, based on measurements performed during the last 12 dialysis sessions); participation in other clinical studies; blood transfusion within the last 3 weeks; deferoxamine treatment within the last 3 months; or anaemia due to other diseases but renal Baseline characteristics Number (analysed/randomised): intervention group (9/9); control group (7/10) (it was reported that "one patient chose to not want to participate" but it was not clear in which group he was) Mean age, range (years): intervention group (49.1, 25 to 70); control group (43.4, 22 to 57) Sex (M/F): treatment group (7/2); control group (6/4) Dialysis type: HD Dialysis vintage (years) (mean ± SD): not reported Comorbidities CVD: not reported Diabetes: not reported Hypertension: not reported Depression (clinician diagnosis): not reported
Interventions	Intervention classification Pharmacological intervention Indication: study targeting fatigue Intervention group rHu‐EPO: 50 IU/kg IV 3 times/week (EPO 5000 IE/mL, diluted in a buffer solution) Control group Placebo (buffer solution) Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available Change in laboratory results (B‐Hb, erythrocytes, mean erythrocyte cell volume, mean erythrocyte cell HCT, S‐transferrin, S‐haptoglobin, vitamin B12, S‐iron, S‐ferritin, reticulocytes, leucocytes and differentiation, thrombocytes, S‐potassium, S‐sodium, S‐carbamide, S‐creatinine, ALAT, S‐bilirubin (total), S‐gamma‐glutamyl transferase, S‐alkaline phosphatase, S‐calcium, S‐phosphate, B‐glucose, S‐protein and bleeding time measurement a.m. Ivy): assessed at weeks 0, 4 and 8 BP (SBP and DBP): assessed until the end of the study Weight: assessed until the end of the study Adverse events: assessed until the end of the study HRQoL Questionnaire (name not reported) (13 symptoms had a score between 0 to 10 was then calculated (0 to 130 points)): assessed at 0 and 8 weeks Perception of severity Frequency Duration Sleep disorders Medication Daily life QoL Fatigue Cramps Rashed Shortness of breath Headache Joint pain Muscle fatigue/weakness Nausea Emesis Angina pectoris Dizziness Palpitation
Notes	Additional information Funding: not reported Conflicts of interest/disclosures: not reported Trial registration identification number: not applicable A priori published protocol: not reported Not English
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Sequence generation methods were not reported in sufficient detail to permit judgement
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "The design of the study was a double blinded, placebo‐controlled study with a duration of eights weeks." Comment: Although author reported that the study used a double‐blind design, information about blinding of participants and investigators were not clearly stated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "In order to investigate the effect of the treatment methods on the patients’ quality of life, a structured interview was performed before and after the study, where the interviewer (the same person for all patients), based upon the patients answers given, calculated a score for the most common complaints that can be seen among haemodialysis patients. [...] Neither the patient, nor the interviewer, saw the results from week 0 during the week 8 interview." Comment: The outcomes were assessed with an appropriate measure, without differences between groups. However, subjective measures were used, it was not stated whether outcomes were assessed without knowledge of treatment allocation, and knowledge of treatment assignment may have influenced reporting. Participant beliefs about the superiority/inferiority of either intervention could have influenced their assessment of the outcome, but there was no evidence that this was likely. However, objective and subjective outcomes were assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "19 adult haemodialysis patients in stable phase. The study was sent to and accepted by the regional ethical research committee. One patient chose to not want to participate. [...] All patients in the EPO‐group completed their study. In the placebo group, three patients had to be excluded due to need of blood transfusion at week 3 (2) and week 5 (1)." Comment: 9/9 participants in the intervention group and 7/10 participants in the control group completed the study (> 5% lost to follow‐up, with differences between groups)
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan were not reported. Fatigue was reported using multiple eligible outcome measurements (scales, time points). Fatigue was reported in a format that was extractable for meta‐analysis. All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	Unclear risk	No sufficient data were available to assess the possible imbalance between groups. Funding and conflicts of interest were not reported