Akizawa Tadao, Origasa Hideki, Kameoka Chisato, Kaneko Yuichiro, Kanoh Hiroyuki
Division of Nephrology, Department of Medicine, Showa University School of Medicine, Toyama, Japan.
Ther Apher Dial. 2014 Jun;18 Suppl 2:24-32. doi: 10.1111/1744-9987.12202.
Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer (Kiklin® Capsules) is a non-absorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study was a multicenter, double-blind, randomized, placebo-controlled study to confirm the superiority of bixalomer to placebo for a 4-week treatment period in patients with chronic kidney disease on hemodialysis with hyperphosphatemia. Sevelamer hydrochloride (HCl), a similar non-absorbable polymer, was used as an active comparator for open-label as a reference without statistical comparison for efficacy and safety. The primary endpoint was the change in serum phosphorus level from baseline. The safety profile was also investigated. The number of subjects was 32 in the placebo group and 31 in each bixalomer group (1.5, 3.0 and 4.5 g/day), respectively. The baseline serum phosphorus level was 7.95 to 8.25 mg/dL. Bixalomer showed a significant decrease in serum phosphorus level at all doses compared with placebo, and the adjusted mean change in serum phosphorus level from the baseline to the end of treatment (at Week 4 or at the time of discontinuation) was +0.24 mg/dL in the placebo group, -0.75 mg/dL in the 1.5 g/day group, -1.32 mg/dL in the 3.0 g/day group, and -1.80 mg/dL in the 4.5 g/day group, showing a dose-dependent decrease in serum phosphorus level. The mean change in serum phosphorus level was -2.32 mg/dL in the sevelamer HCl group under the mean dose of 4.8 g/day. Major adverse events included constipation, hard feces, vomiting, etc.; however, none of the adverse events were serious or severe. Consequently, the superiority of bixalomer to placebo and its dose-dependency for treating hyperphosphatemia were confirmed (Clinical trial registration: NCT00505037).
高磷血症是慢性肾脏病发病和死亡的一个预后因素。比沙洛美（Kiklin®胶囊）是一种不被吸收的聚合物，通过在胃肠道结合磷酸盐来降低血清磷酸盐水平。本研究是一项多中心、双盲、随机、安慰剂对照研究，旨在证实比沙洛美在4周治疗期内对接受血液透析且伴有高磷血症的慢性肾脏病患者优于安慰剂。盐酸司维拉姆，一种类似的不被吸收的聚合物，用作开放标签的活性对照物作为参考，但未对疗效和安全性进行统计学比较。主要终点是血清磷水平相对于基线的变化。同时也对安全性进行了研究。安慰剂组有32名受试者，比沙洛美各剂量组（1.5、3.0和4.5克/天）分别有31名受试者。基线血清磷水平为7.95至8.25毫克/分升。与安慰剂相比，比沙洛美在所有剂量下血清磷水平均显著降低，从基线到治疗结束（第4周或停药时）血清磷水平的调整后平均变化在安慰剂组为+0.24毫克/分升，1.5克/天组为-0.75毫克/分升，3.0克/天组为-1.32毫克/分升，4.5克/天组为-1.80毫克/分升，显示出血清磷水平呈剂量依赖性降低。盐酸司维拉姆组在平均剂量4.8克/天的情况下血清磷水平的平均变化为-2.32毫克/分升。主要不良事件包括便秘、硬便、呕吐等；然而，这些不良事件均不严重或危急。因此，证实了比沙洛美治疗高磷血症优于安慰剂及其剂量依赖性（临床试验注册号：NCT00505037）。
