Supplementary Material for: Efficacy and Safety of Sodium Zirconium Cyclosilicate for Treatment of Hyperkalemia: An 11-Month Open-Label Extension of HARMONIZE

Background: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for treatment of hyperkalemia. An open-label extension (OLE) of the ­HARMONIZE study evaluated efficacy and safety of SZC for ≤11 months. Methods: Patients from HARMONIZE with point-of-care device i-STAT K+ 3.5–6.2 mmol/L received once-daily SZC 5–10 g for ≤337 days. End points included achievement of mean serum K+ ≤5.1 mmol/L (primary) or ≤5.5 mmol/L (secondary). Results: Of 123 patients who entered the extension (mean serum K+ 4.8 mmol/L), 79 (64.2%) completed the study. The median daily dose of SZC was 10 g (range 2.5–15 g). The primary end point was achieved by 88.3% of patients, and 100% achieved the secondary end point. SZC was well tolerated with no new safety concerns. Conclusion: In the HARMONIZE OLE, most patients maintained mean serum K+ within the normokalemic range for ≤11 months during ongoing SZC treatment.

背景：环硅酸锆钠（Sodium zirconium cyclosilicate, SZC；曾用名ZS-9）是一种选择性钾离子（K+）结合剂，用于治疗高钾血症。本研究为HARMONIZE研究的开放标签扩展试验（Open-label Extension, OLE），旨在评估SZC最长11个月使用时的疗效与安全性。方法：纳入HARMONIZE研究的受试者，经床旁检测设备i-STAT检测血清钾浓度为3.5~6.2 mmol/L，予每日1次SZC 5~10 g治疗，最长疗程为337天。试验终点为平均血清钾浓度达到≤5.1 mmol/L（主要终点）或≤5.5 mmol/L（次要终点）。结果：共123例受试者进入该扩展试验，其基线平均血清钾为4.8 mmol/L，其中79例（64.2%）完成本研究。SZC的中位每日给药剂量为10 g（范围2.5~15 g）。88.3%的受试者达成主要终点，100%的受试者达成次要终点。SZC耐受性良好，未出现新的安全性担忧。结论：在HARMONIZE研究的开放标签扩展试验中，多数受试者在持续接受SZC治疗的最长11个月的治疗周期内，平均血清钾维持在正常血钾范围内。