Sodium Zirconium Cyclosilicate in Hyperkalemia

LanAnh Ngo, Pharmacy Candidate 2015

Hyperkalemia can occur in a variety of disease states including kidney failure, diabetes, and heart failure and can lead to serious complications such as cardiac dysrhythmias leading to ventricular fibrillation, and increased mortality. Current therapies for the treatment of hyperkalemia can lead to other complications. 1 A proposal for a new therapy, sodium zirconium cyclosilicate, may help to reduce the risk and make treatment be safer and more effective.

Sodium Zirconium Cyclosilicate in Hyperkalemia1
Design This is a multicenter, two-stage, double-blind, phase 3, randomized study with 753 patients.
Objective The study investigated whether sodium zirconium cylcosilicate (ZS-9) could lower serum potassium levels in patients with hyperkalemia.
Study Groups Patients with hyperkalemia were to receive either ZS-9 or placebo.
Methods The patients with hyperkalemia received either ZS-9 at a dose of 1.25 g, 2.5 g, 5 g, or 10 g or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14 (maintenance phase).
Duration 21 days
Primary Outcome Measure The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours.
Baseline Characteristics The mean age was 65 years (range, 22 to 93) with 60% of the patients being male, and 86% were white. A total of 74.5% had an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2, 66.7% were receiving renin angiotensin aldosterone system inhibitors, 59.9% had diabetes, and 39.8% had a history of heart failure.
Results At 48 hours, the mean exponential rates of change from baseline per hour were reductions of 0.11% in the group receiving 1.25 g of ZS-9, 0.16% in the group receiving 2.5 g, 0.21% in the group receiving 5 g, and 0.30% in the group receiving 10 g, as compared with a reduction of 0.09% per hour in the placebo group (p <0.001 for the comparison with the three highest-dose groups; p >0.05 for the comparison with the 1.25-g group).
Adverse Events Common Adverse Events: diarrhea (frequency in the initial phase = 1.8% in the ZS-9 group, maintenance phase = 1.7%)
Serious Adverse Events: cardiac disorders = 1.5%, general disorders and administration site conditions = 2.2%, Injections and infestations = 1.8%, blood potassium increase = 1.8%, gout = 1.6%, loss of consciousness = 1.5%, hospitalization = 1.5%, respiratory, thoracic, and mediastinal disorders = 1.8%
Percentage that Discontinued due to Adverse Events: 1.5%
Study Author Conclusions There is a significant reduction in potassium levels at 48 hours with normokalemia maintained during 12 days of maintenance therapy in patients with hyperkalemia who received ZS-9 as compared to those who received placebo.

Pending approval, sodium zirconium cyclosilicate may be a viable option for the treatment of hyperkalemia. Future studies should aim to compare with other cation exchange resins such as sodium polystyrene sulfonate to assess superiority or inferiority.


  1. Packham D, Rasmussen H, Lavin P, El-Shahawy M, Roger S, Block G, et al. Sodium Zirconium Cyclosilicate in Hyperkalemia. N Engl J Med 2015; 372:222-31.

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