Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study.
In a 12-month open-label phase 3 trial, individualized once-daily sodium zirconium cyclosilicate maintained normokalemia in most hyperkalemic outpatients without substantial changes to renin-angiotensin-aldosterone system inhibitor therapy.
Background
Oral sodium zirconium cyclosilicate is a selective cation exchanger that binds and removes potassium in the gastrointestinal tract, providing an option for chronic management of hyperkalemia, which is common in patients with chronic kidney disease, heart failure, and those treated with renin-angiotensin-aldosterone system (RAAS) inhibitors.
Study design
This two-part, open-label phase 3 trial enrolled 751 adult outpatients with plasma potassium of at least 5.1 mmol/L. In the correction phase, participants received sodium zirconium cyclosilicate 10 g three times daily for 24 to 72 hours until normokalemic, then entered a maintenance phase of up to 12 months receiving 5 g once daily titrated to maintain normokalemia, without dietary or medication restrictions. The cohort was predominantly older (age 65 or above), with 74% having an eGFR below 60 ml/min per 1.73 m2 and 65% using RAAS inhibitors.
Key findings
During the correction phase, 746 of 751 participants (99%) achieved normokalemia (mean serum potassium 4.8 mmol/L), and 466 (63%) completed the 12-month trial. Over months 3 to 12, mean serum potassium was 4.7 mmol/L, with 88% and 99% of participants maintaining values at or below 5.1 and 5.5 mmol/L, respectively. Among baseline RAAS inhibitor users, 87% continued or increased their dose while 11% discontinued. Serious adverse events occurred in 22% of participants; of eight deaths, none were considered treatment-related, and hypokalemia below 3.0 mmol/L occurred in 1%.
Clinical implications
After correction of hyperkalemia, individualized once-daily sodium zirconium cyclosilicate maintained normokalemia for up to 12 months in the majority of outpatients without requiring substantial reductions in RAAS inhibitor therapy, supporting its role in chronic potassium management while preserving guideline-directed RAAS inhibition.
Category
Research
Source
CJASN
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