BUDAPEST, Hungary — A highly selective potassium-removing agent, sodium zirconium cyclosilicate (SZC) (Lokelma, AstraZeneca), effectively treats hyperkalemia in patients with end-stage renal disease (ESRD) who are receiving hemodialysis, new findings indicate.
Previous studies have shown that SZC is effective in the treatment of hyperkalemia — it was approved for this indication in the United States just over a year ago — but patients receiving dialysis were excluded from earlier studies.
"We recognize that hyperkalemia is very prevalent among hemodialysis patients in the ESRD population and that despite the use of hemodialysis, it remains a very common problem and one that is associated with bad outcomes, including hospitalization, cardiac arrhythmias, and death," Steven Fishbane, MD, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, told delegates here at the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) 56th Congress.
"DIALIZE is the first, randomized, placebo-controlled trial to evaluate the efficacy and safety of SZC in the treatment of hyperkalemia in patients who were on dialysis, and it did meet its primary endpoint, with a large difference in response compared to placebo, and was well tolerated with most adverse events being very similar to [those] in the placebo group," he added.
The study was also published online June 14 in the Journal of the American Society of Nephrology.
SZC Dose Titrated Up During Study
DIALIZE enrolled 196 adults with ESRD who were receiving hemodialysis three times a week and who had hyperkalemia before undergoing dialysis. Hyperkalemia was defined as a serum potassium concentration >5.4 mmol/L after the long interdialytic interval on day –7, as well as a predialysis serum potassium contration >5.0 mmol/L after at least one short interdialytic interval on days –5 and –3.
The prevalence and severity of hyperkalemia are highest after the long interdialytic interval, the longest number of days between dialysis sessions.
Patients received either SZC at a dose of 5 g once a day on nondialysis days or placebo.
The dose of active drug was titrated in 5-g increments over a dose adjustment period of 4 weeks to attain normal potassium levels. Normokalemia was defined as achieving and maintaining a predialysis serum potassium concentration of 4.0 – 5.0 mmol/L after the long interdialytic interval.
The maximum dose of SZC received was 15 g once a day on nondialysis days.
"Treatment was maintained at a stable dose during the 4-week evaluation period," the investigators observe.
The primary outcome measure was the proportion of patients who maintained predialysis serum potassium levels of 4.0 – 5.0 mmol/L during at least three of four hemodialysis sessions after the long interdialytic interval and who did not require rescue medication to reduce serum potassium levels.
"Of the 97 patients who received SZC, 41.2% met the primary endpoint, compared to only 1% out of 99 patients on placebo, for an OR [odds ratio] of 68.8, which was highly statistically significant," Fishbane reported (P < .001).
Changes in serum potassium began to occur during the dose titration phase with SZC, he added, with potassium levels dropping to 5.4 mmol/L and then to approximately 5.1 mmol/L by the end of the dose adjustment phase.
During the evaluation period, "the potassium concentration remained steady at about 5.0 mmol/L, and then after stopping SZC, there was a rapid increase in potassium values predialysis from approximately 5.0 to 5.8 mmol/L," Fishbane observed.
The percentage of patients who required rescue therapy to reduce serum potassium during the overall treatment period was low, at 2.1% for SZC recipients and 5.1% for placebo control patients.
Fishbane noted that the need for rescue medication occurred mostly during the dose adjustment period.
"Most adverse events (AEs) reported were mild or moderate in intensity," the investigators observe.
The most common AEs were gastrointestinal disorders, reported by 19.8% of the SZC group and 17.2% of placebo control patients.
Infections were relatively common, occurring in 12.5% of SZC patients and in 9.1% of placebo patients. Serious AEs occurred in only 7.3% of patients who received active treatment, vs 8.1% of placebo control patients.
Predialysis hypokalemia occurred in five patients in each of the two groups. No cardiac changes were noted, Fishbane pointed out.
"In the phase 3b DIALIZE study, SZC was effective in reducing sK+ [serum potassium] in patients on HD [hemodialysis]. The safety profile of SZC observed in patients managed by HD was similar to that known in the nondialysis population and raised no new concerns," he and his coauthors conclude.
However, they caution that DIALIZE was relatively short in duration and that additional studies are needed to confirm that SZC remains safe and effective in a dialysis population over a longer treatment interval.
European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) 56th Congress.
J Am Soc Nephrol. Published online June 14, 2019. Full text
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