RCT

HARMONIZE

Effect of Sodium Zirconium Cyclosilicate on Potassium in Patients with Hyperkalemia

JAMA, 2014 · Multicenter double-blind randomized trial (n=258)

Clinical question

Does sodium zirconium cyclosilicate (ZS-9 / Lokelma) rapidly restore and maintain normokalemia in outpatient and hospitalized hyperkalemia?

Population: Patients with serum potassium >= 5.1 mEq/L
Intervention: Sodium zirconium cyclosilicate (ZS-9) 10 g three times daily for 48 h, then randomized to 5g, 10g, 15g or placebo daily for 28 days
Comparator: Matching placebo
Primary outcome: Mean serum potassium level during days 8-28
Result: Normokalemia was achieved in 84% at 24 hours and 98% at 48 hours. During maintenance, all ZS-9 doses maintained significantly lower potassium than placebo (P<0.001) with low adverse event rates.

What the trial found

ZS-9 acts within 1-2 hours to reliably bind intestinal potassium and achieve normokalemia without causing colonic necrosis.

Current guideline position

Recommended in UKKA 2023 and KDIGO hyperkalemia guidance.

Clinical interpretation

Supported modern non-absorbed potassium binder therapy over sodium polystyrene sulfonate (Kayexalate).

Clinical Context & Relevant Topics (1)

Disease Reference

Severe Hyperkalemia in Critical Illness

Nernst resting potential mechanics, ECG progression, the 3-step resuscitation framework (Stabilize, Shift, Eliminate), and post-dialysis rebound kinetics.

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