Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study

• Published in: Clinical journal of the American Society of Nephrology 2019-06, Vol.14 (6), p.798-809
• Main Authors: Spinowitz, Bruce S, Fishbane, Steven, Pergola, Pablo E, Roger, Simon D, Lerma, Edgar V, Butler, Javed, von Haehling, Stephan, Adler, Scott H, Zhao, June, Singh, Bhupinder, Lavin, Philip T, McCullough, Peter A, Kosiborod, Mikhail, Packham, David K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Humans; Hyperkalemia - blood; Male; Original; Potassium - blood; Renin-Angiotensin System - drug effects; Silicates
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.12651018

Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial. In the correction phase, adult outpatients with plasma potassium ≥5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24-72 hours until normokalemic (potassium =3.5-5.0 mmol/L). Qualifying participants entered the ≤12-month maintenance phase and received sodium zirconium cyclosilicate 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions. Prespecified primary end points were restoration of normal serum potassium values (3.5-5.0 mmol/L) during the correction phase and maintenance of serum potassium ≤5.1 mmol/L during the maintenance phase. Adverse events were assessed throughout. Of 751 participants, 746 (99%) achieved normokalemia during the correction phase (mean serum potassium =4.8 mmol/L; 95% confidence interval, 4.7 to 4.8) and entered the maintenance phase; 466 (63%) participants completed the 12-month trial. Participants were predominantly white, men, and age ≥65 years old; 74% had an eGFR