Randomized equivalence study evaluating the possibility of switching hemodialysis patients receiving subcutaneous human erythropoietin directly to intravenous darbepoetin alfa.

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used either intravenously or subcutaneously with no dose penalty; however, the direct switch from subcutaneous recombinant human erythropoietin (rHuEPO) to intravenous darbepoetin has barely been studied. OBJECTIVE: To establish the equivalence of a direct switch from subcutaneous rHuEPO to intravenous darbepoetin versus an indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin in patients undergoing hemodialysis. METHODS: In this open, randomized, 6-month, prospective study, patients with end-stage kidney disease who were on hemodialysis were randomized into 2 groups: direct switch from subcutaneous rHuEPO to intravenous darbepoetin (group 1) and indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin (group 2). A third, nonrandomized group (control), consisting of patients treated with intravenous rHuEPO who were switched to intravenous darbepoetin, was also studied to reflect possible variations of hemoglobin (Hb) levels due to change from one type of ESA to the other. The primary outcome was the proportion of patients with stable Hb levels at month 6. Secondary endpoints included Hb stability at month 3, dosage requirements for darbepoetin, and safety of the administration route. RESULTS: Among 154 randomized patients, the percentages with stable Hb levels were equivalent in groups 1 and 2, respectively, at month 3 (86.0% vs 91.3%) and month 6 (82.1% vs 81.6%; difference -0.5 [90% CI -12.8 to 11.8]). Mean Hb levels between baseline and month 6 remained stable in both groups, with no variation in mean darbepoetin dose. Mean ferritin levels remained above 100 microg/L in the 3 groups during the whole study, and darbepoetin was well tolerated. CONCLUSIONS: This study has shown equivalent efficacy on Hb stability without the need for dosage increase in patients switched directly from subcutaneous rHuEPO to intravenous darbepoetin.