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

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K&lt;sup&gt;+&lt;/sup&gt;) binder for treatment of hyperkalemia. An open-label extension (OLE) of the ­HARMONIZE study evaluated efficacy and safety of SZC for ≤11 months. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients from HARMONIZE with point-of-care device i-STAT K&lt;sup&gt;+&lt;/sup&gt; 3.5–6.2 mmol/L received once-daily SZC 5–10 g for ≤337 days. End points included achievement of mean serum K&lt;sup&gt;+&lt;/sup&gt; ≤5.1 mmol/L (primary) or ≤5.5 mmol/L (secondary). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 123 patients who entered the extension (mean serum K&lt;sup&gt;+&lt;/sup&gt; 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. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; In the HARMONIZE OLE, most patients maintained mean serum K&lt;sup&gt;+&lt;/sup&gt; within the normokalemic range for ≤11 months during ongoing SZC treatment.</jats:p

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

Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE

Abstract Background Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC. Methods Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK+) concentrations of 4.0–5.0 and 4.0–5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK+ and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to &lt; 2, 2 to &lt; 3, 3 to &lt; 4, and ≥ 4 mmol/L). Results A greater proportion of patients achieved the ranges of pre-dialysis sK+ concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK+ concentrations of 4.0–5.0 and 4.0–5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was − 0.74 mmol/L (− 0.97 to − 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo. Conclusions These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients. Trial registration NCT03303521. </jats:sec