Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

Background. Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. Methods. Adults with serum K+ >= 5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5g for <= 12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or >= 30 mL/min/1.73 m(2)). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). Results. Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, >= 30mL/min/1.73m(2) or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24h, and 100 and 95% with baseline eGFR <30 and >= 30mL/min/1.73m(2), respectively, within 72h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 >= 30mL/min/1.73m(2) subgroup. Conclusions. SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Automated summary

The study demonstrated that sodium zirconium cyclosilicate effectively reduces serum potassium levels in patients with hyperkalaemia, and is beneficial for maintaining normokalaemia during the maintenance phase. Adverse events were more common in patients with severe impairment of kidney function.