OBJECTIVE To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb) maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO). METHODS This was an open, randomized, controlled, multi-center trial. All the hemodialysis or peritoneal dialytic patients in EPO maintenance
treatment received subcutaneous EPO- during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L. Eligible patients were randomized (2:1) to accept either C.E.R.A. once every 4 weeks by subcutaneous administration (C.E.R.A. group, n = 187) or subcutaneous EPO- 1-3 times weekly (EPO group, n = 94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period). The starting dose of C.E.R.A. was converted according to the dose of EPO- administered in the week preceding the first study drug administration. The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period. RESULTS Totally 253 patients completed the whole 28-week treatment. The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A. group and +1.23 g/L for EPO group, resulting in a treatment difference of 1.34 g/L (95%CI -1.11 - 3.78 g/L). Since the lower limit of 95%CI was greater than the pre-defined non-inferiority margin -7.5 g/L (P < 0.0001), C.E.R.A. once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level. The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups (69.0% for C.E.R.A. group vs 68.9% for EPO group, P > 0.05). The overall incidence of adverse events was similar between the C.E.R.A.(41.7%) and EPO (46.2%) groups (P > 0.05). The safety findings were in accordance with the patients' primary diseases rather than the administration. CONCLUSIONS Conversion from EPO to C.E.R.A. once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia, and it was non-inferior to EPO. In general, subcutaneous administration of C.E.R.A. is well tolerated in dialytic patients with chronic renal anemia.