Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled HARMONIZE-Global study
Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled HARMONIZE-Global study
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DOI：
10.1002/ehf2.12561
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发表时间：
2020-01-15
影响因子：
3.8
通讯作者：
Zhao, June
中科院分区：
文献类型：
--
作者：
Zannad, Faiez;Hsu, Bang-Gee;Zhao, June
目的环硅酸锆钠（SZC，以前的ZS-9）是一种选择性K+结合剂，用于治疗成人高钾血症。HARMONIZE-Global在来自不同地理和种族的高钾血症门诊患者中检查了SZC的疗效和安全性。方法和结果这项III期、随机、双盲、安慰剂对照研究在日本、俄罗斯、韩国和中国台湾的45个研究中心招募了血清K+ >= 5.1 mmol/L（通过床旁i-STAT设备测量）的门诊患者。在48小时纠正期（CP）内接受每日3次SZC 10 g开放标签治疗后，在28天维持期（MP）内将达到正常钾血症（K+ 3.5-5.0 mmol/L）的患者以2：2：1的比例随机分配至每日1次SZC 5 g、SZC 10 g或安慰剂组。主要终点为MP第8-29天的中心实验室平均K+水平。在CP的267例患者中，248例（92.9%）进入MP。CP期间，48 h时中心实验室K+平均值较基线降低1.28 mmol/L（P < 0.001）。在MP期间（第8-29天），与安慰剂相比，SZC 5和10 g每日一次分别使中心实验室K+平均值显著降低9.6%和17.7%（两者均P < 0.001）。与安慰剂组（24.0%）相比，SZC 5（58.6%）和10 g（77.3%）组中有更多患者出现血钾正常（第29天中心实验室K+ 3.5-5.0 mmol/L），10 g组中血钾正常天数最多。SZC最常见的不良事件是轻度或中度便秘和水肿。结论：对门诊高钾血症患者，使用SZC治疗后，CP期间达到的正常血钾可维持28天以上。
Aims Sodium zirconium cyclosilicate (SZC, formerly ZS-9) is a selective K+ binder to treat adults with hyperkalaemia. HARMONIZE-Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins. Methods and results This phase 3, randomized, double-blind, placebo-controlled study recruited outpatients with serum K+ >= 5.1 mmol/L (measured by point-of-care i-STAT device) at 45 sites in Japan, Russia, South Korea, and Taiwan. Following open-label treatment with thrice-daily SZC 10 g during a 48 h correction phase (CP), patients achieving normokalaemia (K+ 3.5-5.0 mmol/L) were randomized 2:2:1 to once-daily SZC 5 g, SZC 10 g, or placebo during a 28 day maintenance phase (MP). The primary endpoint was mean central-laboratory K+ level during days 8-29 of the MP. Of 267 patients in the CP, 248 (92.9%) entered the MP. During the CP, mean central-laboratory K+ was reduced by 1.28 mmol/L at 48 h vs. baseline (P < 0.001). During the MP (days 8-29), SZC 5 and 10 g once-daily significantly lowered mean central-laboratory K+ by 9.6% and 17.7%, respectively, vs. placebo (P < 0.001 for both). More patients had normokalaemia (central-laboratory K+ 3.5-5.0 mmol/L at day 29) with SZC 5 (58.6%) and 10 g (77.3%) vs. placebo (24.0%), with the greatest number of normokalaemic days in the 10-g group. The most common adverse events with SZC were mild or moderate constipation and oedema. Conclusions Normokalaemia achieved during the CP was maintained over 28 days with SZC treatment among outpatients with hyperkalaemia.