한국인 혈액투석 환자의 빈혈 치료에 있어 Darbepoetin Alfa의 유효성 및 안전성에 대한 제 3상 임상시험 = Randomized, Controlled Trial of Darbepoetin Alfa for the Treatment of Renal Anemia in Hemodialysis Patients

다국어 초록 (Multilingual 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 changed 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 µg 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-titration 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.

국문 초록 (Abstract)

목 적:Darbepoetin alfa는 현재 임상에서 상용되고 있는 유전자 재조합 인 에리쓰로포이에틴 (r-HuEPO)과 비교하여 그 반감기가 3배 정도 되는 새로운 조혈제이다. 본 연구에서는 혈액투석 환자의 빈혈 치료에 있어 darbepoetin alfa가 r-HuEPO와 비교하여 투여 간격을 늘여 투여하였을 때 동등한 정도의 효과가 있는지를 알아보고자 하였다.
방 법:r-HuEPO를 정주 또는 피하주사 받고 있는 총 74명의 혈액투석 환자를 대상으로 하여, 그 중 35명은 r-HuEPO를 계속 주사하였고, 39명은 동일한 용법 및 투여 경로로 darbepoetin alfa로 대체하여 투여하였다. r-HuEPO를 주 2-3회 투여받던 환자는 주 1회, r- HuEPO를 주 1회 투여받던 환자에게는 2주에 1회씩 darbepoetin alfa를 투여하였으며, 그 용량은 무작위 배정시의 r-HuEPO의 주당 (또는 2주당) 총 용량을 기초로 해서 r-HuEPO 200 단위=darbepoetin alfa 1 µg의 전환식을 사용하여 결정하였다. r-HuEPO와 darbepoetin alfa의 투여량은 총 20주의 관찰 기간 동안 (16주의 용량 조절기간 후 4주간의 평가 기간) 헤모글로빈을 약제 투여 이전의 개인 기저 헤모글로빈치와 비교하여 -1.0-＋1.5 g/dL를 유지할 수 있도록 조절하였다.
결 과:기저 헤모글로빈 농도와 비교하여 평가 기간의 헤모글로빈의 평균 변화는 darbepoetin alfa 군에서 -0.03±0.19 g/dL, r-HuEPO 군에서 0.27±0.20 g/dL이었다. 따라서 두 군간의 차이는 -0.30 g/dL (darbepoetin alfa 군 - r-HuEPO군; 95% 신뢰구간, -0.84-0.23)로 통계적으로 의미가 없었다. 발생한 이상반응은 두 군에서 비슷하였다.

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