RESUMEN
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-ß 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-ß 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-ß 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.