Nephrology Department, Indiana University Health Arnett, Lafayette, Indiana, USA.
Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Nephron. 2022;146(6):599-609. doi: 10.1159/000523911. Epub 2022 Apr 22.
Sodium zirconium cyclosilicate (SZC) is a selective potassium (K+) binder for hyperkalemia management that provides rapid and sustained correction of hyperkalemia. The NEUTRALIZE study is investigating whether SZC, in addition to correcting hyperkalemia and maintaining normal serum K+, can provide sustained increases in serum bicarbonate (HCO3-) in patients with hyperkalemia and metabolic acidosis associated with chronic kidney disease (CKD).
This is a prospective, randomized, double-blind, placebo-controlled phase 3b study of US adults with stage 3-5 CKD not on dialysis with hyperkalemia (K+ >5.0-≤5.9 mmol/L) and low-serum HCO3- (16-20 mmol/L). In the open-label correction phase, all eligible patients receive SZC 10 g three times daily for up to 48 h. Patients who achieve normokalemia (K+ ≥3.5-≤5.0 mmol/L) are then randomized 1:1 to once-daily SZC 10 g or placebo for a 4-week, double-blind, placebo-controlled maintenance phase. The primary endpoint is the proportion of patients with normokalemia at the end of treatment (EOT) without rescue therapy for hyperkalemia. Key secondary endpoints include mean change in serum HCO3-, the proportion of patients with an increase in serum HCO3- of ≥2 or ≥3 mmol/L without rescue therapy for metabolic acidosis, and the proportion of patients with serum HCO3- ≥22 mmol/L at EOT.
NEUTRALIZE will establish whether SZC can provide sustained increases in serum HCO3- while lowering serum K+ in patients with hyperkalemia and CKD-associated metabolic acidosis and may provide insights on the mechanism(s) underlying the increased serum HCO3- with SZC treatment.
硅酸锆酸钠（SZC）是一种用于高钾血症管理的选择性钾（K+）结合剂，可快速持续纠正高钾血症。NEUTRALIZE 研究旨在探讨 SZC 是否除了纠正高钾血症和维持正常血清 K+外，还能否为伴有慢性肾脏病（CKD）的高钾血症和代谢性酸中毒的患者提供持续升高的血清碳酸氢盐（HCO3-）。
这是一项在美国未接受透析的 3-5 期 CKD 成人中进行的前瞻性、随机、双盲、安慰剂对照的 3b 期研究，这些患者患有高钾血症（K+>5.0-≤5.9 mmol/L）和低血清 HCO3-（16-20 mmol/L）。在开放标签校正阶段，所有符合条件的患者接受 SZC 10 g 每日三次，最多 48 小时。达到正常血钾（K+≥3.5-≤5.0 mmol/L）的患者随后随机 1:1 接受每日一次 SZC 10 g 或安慰剂治疗 4 周，进入双盲、安慰剂对照的维持阶段。主要终点是治疗结束（EOT）时无需高钾血症抢救治疗的患者达到正常血钾的比例。关键次要终点包括血清 HCO3-的平均变化、无需代谢性酸中毒抢救治疗而血清 HCO3-增加≥2 或≥3 mmol/L的患者比例、以及 EOT 时血清 HCO3-≥22 mmol/L的患者比例。
NEUTRALIZE 将确定 SZC 是否可以在伴有高钾血症和 CKD 相关代谢性酸中毒的患者中提供持续升高的血清 HCO3-，同时降低血清 K+，并可能为 SZC 治疗导致血清 HCO3-升高的机制提供见解。
