Vanrenterghem Yves, Bárány Peter, Mann Johannes F E, Kerr Peter G, Wilson Janet, Baker Nigel F, Gray Stephen J
Department of Nephrology, University Hospital Leuven, Leuven, Belgium.
Kidney Int. 2002 Dec;62(6):2167-75. doi: 10.1046/j.1523-1755.2002.00657.x.
Darbepoetin alfa is a glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). We aimed to determine whether darbepoetin alfa is as effective and well tolerated as rHuEPO for treating renal anemia in dialysis patients when administered at a reduced dose frequency.
A total of 522 European and Australian hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized, open-label in a 1:2 ratio to continue rHuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dose frequency. Patients receiving rHuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving rHuEPO two or three times weekly changed to once-weekly darbepoetin alfa. The doses of rHuEPO and darbepoetin alfa were titrated to maintain hemoglobin close to the patient's baseline level for up to 52 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period at weeks 25 to 32 of treatment.
The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (-0.03 g/dL; SE 0.11) and rHuEPO (-0.06 g/dL; SE 0.13) groups, and the difference between the two treatments was 0.03 g/dL (95% CI -0.16, 0.21). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. At the end of the evaluation period, >/=95% of patients had their hemoglobin successfully maintained on their assigned dose frequency for darbepoetin alfa (once weekly and once every other week) and rHuEPO (once, twice and three times weekly). The safety profiles of darbepoetin alfa and rHuEPO were similar, and no antibodies to either treatment were detected.
Darbepoetin alfa maintains hemoglobin as effectively as rHuEPO, but with a reduced dose frequency.
达比加群酯是一种糖蛋白，其末端半衰期比重组人促红细胞生成素（rHuEPO）长三倍。我们旨在确定当以降低的给药频率给药时，达比加群酯在治疗透析患者肾性贫血方面是否与rHuEPO一样有效且耐受性良好。
共有522名通过静脉（IV）或皮下（SC）途径接受稳定rHuEPO治疗的欧洲和澳大利亚血液透析及腹膜透析患者，以1:2的比例随机、开放标签分组，继续使用rHuEPO或接受同等剂量但给药频率降低的达比加群酯。接受每周一次rHuEPO治疗的患者改为每两周一次达比加群酯，接受每周两次或三次rHuEPO治疗的患者改为每周一次达比加群酯。rHuEPO和达比加群酯的剂量进行滴定，以在长达52周的时间内将血红蛋白维持在接近患者基线水平。主要终点是治疗第25至32周基线与评估期之间血红蛋白的变化。
达比加群酯组（-0.03 g/dL；标准误0.11）和rHuEPO组（-0.06 g/dL；标准误0.13）从基线到评估期血红蛋白的平均变化相似，两种治疗之间的差异为0.03 g/dL（95%CI -0.16，0.21）。尽管达比加群酯的给药频率降低，但这在统计学上并非显著差异，也无临床相关性差异。在评估期结束时，≥95%的患者在其分配的达比加群酯给药频率（每周一次和每两周一次）和rHuEPO给药频率（每周一次、两次和三次）下成功维持了血红蛋白水平。达比加群酯和rHuEPO的安全性概况相似，未检测到针对任何一种治疗的抗体。
达比加群酯在维持血红蛋白方面与rHuEPO同样有效，但给药频率降低。
