一项比较肝素接枝膜加含柠檬酸盐透析液与局部枸橼酸抗凝的非劣效性试验：CiTED 研究结果。

A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: results of the CiTED study.

机构信息

Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.

Division of Nephrology, UZ Leuven, Leuven, Belgium.

出版信息

Nephrol Dial Transplant. 2017 Apr 1;32(4):707-714. doi: 10.1093/ndt/gfw461.

DOI:10.1093/ndt/gfw461

PMID:28407129

Abstract

BACKGROUND

Anticoagulation is a prerequisite for successful haemodialysis. Heparin and low-molecular weight heparins are routinely used despite increased bleeding risk. Regional citrate anticoagulation (RCA) is efficacious, but is laborious and may induce metabolic disturbances. Heparin-grafted membranes are less efficacious. It is not known whether combining citrate-containing dialysate and a heparin-grafted membrane is a valid anticoagulation strategy.

METHODS

We performed a randomized crossover noninferiority trial, with a prespecified noninferiority threshold of 10% in maintenance dialysis patients ( n = 25). We compared the combination of citrate-containing dialysate plus a heparin-grafted membrane [CiTrate and EvoDial (CiTED) protocol] with RCA. The primary endpoint was completion of dialysis without significant clotting. Secondary endpoints included time to clotting, achieved Kt / V urea , loss of total cell volume, venous air chamber clotting score and systemic-ionized calcium concentration.

RESULTS

In total, 1284 sessions were performed according to study protocol, 636 in the CiTED arm and 648 in the RCA arm. The primary outcome of preterm interruption due to clotting occurred in 36 (5.7%) of sessions in the CiTED arm, and in 40 (6.2%) sessions in the RCA arm, thereby meeting noninferiority criteria (P < 0.0001). Most of the clotting events occurred in the fourth hour of dialysis. Repetitive clotting occurred in four patients in the CiTED arm and one patient in the RCA arm. Time to preterm interruption due to clotting and achieved Kt / V urea was not significantly different. Systemic-ionized calcium levels during treatment were significantly lower in the RCA arm and clinically relevant hypocalcaemia was noted only in the RCA arm.

CONCLUSION

The combination of citrate-containing dialysate and a heparin-grafted membrane is a valid alternative to RCA.

摘要

背景

抗凝是成功血液透析的前提。肝素和低分子肝素尽管增加了出血风险，但仍被常规使用。局部枸橼酸抗凝（RCA）是有效的，但繁琐且可能引起代谢紊乱。肝素接枝膜的效果较差。目前尚不清楚在含有枸橼酸盐的透析液和肝素接枝膜联合使用是否是一种有效的抗凝策略。

方法

我们进行了一项随机交叉非劣效性试验，在维持性透析患者（n=25）中预设了 10%的非劣效性阈值。我们比较了含有枸橼酸盐的透析液加肝素接枝膜[枸橼酸和 EvoDial（CiTED）方案]与 RCA 的组合。主要终点是无明显凝血完成透析。次要终点包括凝血时间、达到的 Kt/V 尿素、总细胞体积损失、静脉空气室凝血评分和系统离子钙浓度。

结果

根据研究方案共进行了 1284 次透析，CiTED 组 636 次，RCA 组 648 次。CiTED 组有 36 次（5.7%）、RCA 组有 40 次（6.2%）因凝血提前中断，符合非劣效性标准（P<0.0001）。大多数凝血事件发生在透析的第四个小时。CiTED 组有 4 例和 RCA 组有 1 例重复发生凝血。凝血提前中断时间和达到的 Kt/V 尿素无显著差异。治疗期间，RCA 组的系统离子钙水平明显较低，仅在 RCA 组出现临床相关的低钙血症。