Sodium zirconium cyclosilicate post hospital discharge to prevent hyperkalaemia: phase 4, randomized CONTINUITY trial

Abstract Background and Hypothesis Hyperkalaemia is common and potentially life-threatening in individuals with chronic kidney disease (CKD). While sodium zirconium cyclosilicate (SZC) is used in the hospital setting for hyperkalaemia management, few patients are discharged with a continuing prescription, leaving them at risk of recurrent hyperkalaemia and rehospitalization. The CONTINUITY study aimed to establish the efficacy of continuing post-hospital discharge treatment with SZC versus standard of care (SOC) in maintaining normokalaemia and reducing all-cause and hyperkalaemia-related hospital admissions and emergency department visits in patients with CKD and hyperkalaemia. Methods This phase 4, randomized, controlled, open-label, parallel-group, multicentre study 28 sites; six European countries; 24 March 2022–10 December 2024) included participants aged ≥ 18 years admitted to hospital with diagnosed CKD (any stage) and hyperkalaemia [serum potassium (sK+) > 5.0 and ≤ 6.5 mmol/L] without ongoing K+ binder treatment. Participants received SZC for 2–21 days to normalize sK+. Those with normokalaemia (3.5–5.0 mmol/L) at discharge were randomized to SZC or SOC. The primary objective was occurrence of normokalaemia at 180 days post-discharge [those achieving normokalaemia (responders) vs those who did not (non-responders)]. Results The difference between arms for normokalaemia responders was not statistically significant: 30.9% (SZC) and 36.2% (SOC) (odds ratio 0.81; 95% CI 0.39–1.66; P = 0.558). High and imbalanced levels of missing sK+ measurements at 180 days (n = 35 [51.5%] in the SZC arm and n = 25 [36.2%] in the SOC arm) led to substantially lower levels of normokalaemia response than the original assumptions in the sample size calculations used to power the study. Conclusion The study did not meet its primary endpoint. Study design limitations may have masked true treatment effects. Post hoc analyses revealed positive trends in SZC use and potential for reducing rehospitalization and enabling renin-angiotensin-aldosterone system inhibitor therapy continuation at optimal doses.