한국인 혈액투석 환자의 빈혈 치료에 있어 darbepoetin alfa의 유효성 및 안전성에 대한 제 3상 임상시험

Abstract

Background: Darbepoetin alfa is a new erythropoietic agent with a three fold longer terminal half-life than recombinant human erythropoietin (r-HuEPO). The aim of this randomized, open-label study is to determine whether darbepoetin alfa is as effective as r-HuEPO for the treatment of anemia in hemodialysis patients when administered at a reduced dosing frequency.

Methods: A total 74 Korean hemodialysis patients receiving r-HuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized to continue r-HuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dosing frequency. Patients receiving r-HuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving r-HuEPO two or three times weekly chaged to once-weekly darbepoetin alfa. The initial dose of darbepoetin alfa was based on the r-HuEPO dose at the time of entry into the study, using a formula equating the peptide mass of the two molecules (200 IU r-HuEPO=1 ㎍ darbepoetin alfa). The doses of r-HuEPO and darbepoetin alfa were titrated to maintain hemoglobin concentrations within –1.0 to +1.5 g/dL of patients’ baseline values and within a range of 8.0 to 13.0 g/dL for up to 20 weeks (16-week dose-titratio period followed by a 4- week evaluation period). The primary end point was change in hemoglobin level between baseline and the evaluation period.

Results: The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (–0.03±0.19 g/dL) and r-HuEPO (0.27±0.20 g/dL) groups, and the difference between the two treatments was –0.30 g/dL (95% CI, -0.84 to 0.23). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. The safety profiles of darbepoetin alfa and r-HuEPO were similar.

Conclusion: This study suggests that darbepoetin alfa maintains hemoglobin as effectively as r-HuEPO, but with reduced dose frequency.