Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients.
Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients.
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DOI：
10.1093/ndt/gfv277
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Gupta A
中科院分区：
文献类型：
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作者：
Fishbane SN;Singh AK;Cournoyer SH;Jindal KK;Fanti P;Guss CD;Lin VH;Pratt RD;Gupta A
通过血液透析液施用焦磷酸柠檬酸铁（FPC，Tiferic™）可以替代持续的尿毒症和血液透析相关的铁损失。 FPC 将铁直接提供给转铁蛋白，绕过网状内皮系统并避免铁螯合。两项相同的 3 期随机安慰剂对照试验（CRUISE 1 和 2）在 599 名补铁慢性血液透析患者中进行。患者使用含有 2 µM FPC-铁的透析液或标准透析液（安慰剂）进行长达 48 周的透析。禁止口服或静脉补铁，红细胞生成刺激剂的剂量保持恒定。主要疗效终点是血红蛋白 (Hgb) 浓度从基线到治疗结束 (EoT) 的变化。次要终点包括网织红细胞血红蛋白含量（CHr）和血清铁蛋白。在这两项试验中，FPC 组的 Hgb 浓度从基线到 EoT 保持不变，但安慰剂组降低了 0.4 g/dL（P < 0.001，综合结果；95% 置信区间 [CI] 0.2-0.6）。与 FPC 治疗相比，安慰剂治疗导致 CHr（-0.9 pg 与-0.4 pg，P < 0.001）和血清铁蛋白（-133.1 µg/L 与-69.7 µg/L，P < 0.001）相对于基线的平均下降显着更大。两个治疗组中发生不良事件和严重不良事件的患者比例相似。血液透析期间通过透析液输送的 FPC 可以替代铁损失，维持 Hgb 浓度，不会增加铁储存，并且表现出与安慰剂相似的安全性。通过透析液进行血液透析的 FPC 代表了向血液透析患者提供维持铁治疗的范式转变。
Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2–0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (−0.9 pg versus −0.4 pg, P < 0.001) and serum ferritin (−133.1 µg/L versus −69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.