Sodium zirconium cyclosilicate (SZC), a potassium binder, can normalize serum potassium levels between dialysis sessions for maintenance hemodialysis (HD) patients with persistent hyperkalemia, findings from the phase 3b DIALIZE trial show.
Investigators led by Steven Fishbane, MD, of the Zucker School of Medicine at Hofstra/Northwell in Great Neck, New York, randomly assigned 196 patients (mean age 58 years) with serum potassium values exceeding 5.4 mmol/L after the long interdialytic interval (prior to dialysis) to SZC (which exchanges hydrogen and sodium ions for potassium ions in the gastrointestinal lumen) or placebo. SZC was titrated from 5 g up to a maximum 15 g daily on non-dialysis days over the first 4 weeks until a stable dose was established.
The primary end point was the proportion of patients who maintained predialysis serum potassium levels of 4.0 to 5.0 mmol/L during at least 3 long interdialytic intervals in the 1-month evaluation period following dose titration.
A significantly greater proportion of SZC than placebo patients responded to treatment and met the primary end point (41.2% vs 1.0%), Dr Fishbane and his colleagues reported at the 56th European Renal Association-European Dialysis and Transplant Association Congress in Budapest, Hungary, and in the Journal of the American Society of Nephrology.
In addition, half as many SZC patients required rescue therapy to reduce their serum potassium (2.1% vs 5.1%).
Overall, SZC was well tolerated. Serious adverse events occurred in 7% and 8% of patients in the SZC and placebo groups, respectively. Two people in the SZC group had angina pectoris that was considered unrelated to treatment. The most common complaint was gastrointestinal disorders. Interdialytic weight gain was comparable between groups, indicating no excess risk of fluid retention with SZC. Hypokalemia occurred in 5 patients in each group.
DIALIZE is the first randomized, placebo-controlled trial to evaluate a potassium binder in HD patients. “By demonstrating preliminary efficacy and safety for sodium zirconium cyclosilicate, the trial opens a new avenue for controlling hyperkalemia in patients on hemodialysis,” Dr Fishbane told Renal & Urology News. “In subsequent studies, it will be interesting to learn whether SZC treatment permits the relaxation of dietary potassium restrictions or an increase in dialysate potassium concentration.”
The study was relatively short, so longer studies evaluating clinical end points such as hospitalization and cardiovascular events are also needed.
This study was funded by AstraZeneca, the makers of SZC (Lokelma).
Fishbane S, Ford M, Masafumi F, et al. A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia. J Am Soc Nephrol. 2019; published online ahead of print.