Abstract: TH-PO1112

Maintained Efficacy and Safety of Sodium Zirconium Cyclosilicate for Hyperkalemia: 12-Month, Open-Label, Phase 3 Study

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders


  • Fishbane, Steven, Hofstra Northwell Health School of Medicine, Great Neck, New York, United States
  • Adler, Scott H., AstraZeneca, Gaithersburg, Maryland, United States
  • Singh, Bhupinder, ZS Pharma Inc., part of AstraZeneca, San Mateo, California, United States
  • Lavin, Philip T., Boston Biostatistics Research Foundation, Framingham, Massachusetts, United States
  • McCullough, Peter A., Baylor University Medical Center, Dallas, Texas, United States
  • Kosiborod, Mikhail, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, United States
  • Pergola, Pablo E., Renal Associates PA , San Antonio, Texas, United States
  • Packham, David K., University of Melbourne, Melbourne, New South Wales, Australia
  • Roger, Simon D., Renal Research, Gosford, New South Wales, Australia
  • Lerma, Edgar V., UIC/ Advocate Christ, Oak Lawn, Illinois, United States
  • Butler, Javed, Stony Brook University, Stony Brook, New York, United States
  • Von haehling, Stephan, University of Göttingen Medical Centre, Göttingen, Germany
  • Spinowitz, Bruce S., New York-Presbyterian/Queens and Weill Medical College of Cornell University, Flushing, New York, United States
  • Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States

We evaluated sodium zirconium cyclosilicate (ZS), an oral, highly selective potassium (K) binder for hyperkalemia over 12 mo.


This international, multicenter, open-label, single-arm phase 3 trial enrolled 751 outpatients (≥18y) with K≥5.1mEq/L. In acute phase (AP), patients (pts) received 10g ZS TID for 24–72h until K ≤5.0mEq/L by point-of-care device (iSTAT). 746 pts with K 3.5-5.0mEq/L by iSTAT entered an extended phase (EP) and received ZS titrated to K ≤5.0mEq/L (5g to start, min 5g every other day, max 15g daily) for ≤12mo without diet or RAASi restrictions. Primary endpoints were measured by central laboratory: % with normal K acutely; % with K≤5.1 or ≤5.5mEq/L during 3-12mo; mean K; adverse events (AE).


Pts had a median age of 64y, 74% had eGFR <60, 38% had heart failure and 70% were on RAASi. During AP, baseline mean K decreased from 5.6 to 4.8 mEq/L; K 3.5-5.0mEq/L was achieved in 99% and 78% of pts when assessed by i-STAT and central lab, respectively; K 3.5-5.5mEq/L was achieved in 99% (central lab). Overall, 466 (62.5%) completed EP. Mean daily ZS dose was 7.2g. Normokalemia was maintained up to 12 mo [Figure]. During EP, mean K ≤5.1 or ≤5.5mEq/L was achieved in 88% and 99% of pts over 3-12 mo, respectively; 489 (65.5%) pts experienced an AE and 21.6% a serious AE. There were 8 (1.1%) deaths. Common AEs (>5%) were hypertension, peripheral edema, urinary tract infection, constipation, and anemia. Laboratory-determined hypokalemia (<3.5mEq/L) occurred in 5.8% (1.2% with K 2.5-<3.0).


ZS treatment rapidly reduced K in pts with hyperkalemia and maintained normokalemia for up to 12 mo; safety profile was consistent with prior studies and acceptable for this patient population.


  • Commercial Support