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Once-daily ZS-9 improved, maintained serum potassium levels in patients with HF, hyperkalemia
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LAS VEGAS — Patients with hyperkalemia, including those with HF receiving treatment with renin-angiotensin-aldosterone system inhibitors, experienced rapid and sustained reductions in serum potassium levels when treated with sodium zirconium cyclosilicate, according to data presented at the Heart Failure Society of America Annual Scientific Meeting.
In the multicenter, double blind, phase 3 ZS-003 trial, researchers evaluated the safety and efficacy of sodium zirconium cyclosilicate, also known as ZS-9 (ZS Pharma), in 753 patients with hyperkalemia. The patients were randomly assigned to placebo or 1.25 g, 2.5 g or 10 g of ZS-9 three times a day during a 48-hour acute phase, followed by a 12-day maintenance period in which 542 patients who achieved normokalemia during the acute phase were re-randomly assigned to once-daily ZS-9 or placebo for 12 days.
Mohamed El-Shahawy, MD, MPH, and colleagues observed significant, dose-dependent reductions in serum potassium within 48 hours of treatment, which were highly significant in the 5-g and 10-g groups. At 12 days, significantly more treated patients maintained normokalemia compared with placebo (ZS-9 5 g, P=.0075; 10 g, P<.0001).
Mohamed El-Shahawy
The data presented come from a secondary analysis assessing the benefits of once-daily ZS-9 5 g or 10 g vs. placebo for the prevention of hyperkalemia recurrence in patients with HF, including those who were also receiving treatment with a renin-angiotensin-aldosterone system (RAAS) inhibitor.
The 5-g arm included 26 treated patients and 28 placebo recipients with HF; the 10-g arm included 26 treated patients and 23 placebo recipients. Treated patients in both arms maintained normokalemia more frequently than placebo recipients, with significantly lower mean serum potassium levels observed among those receiving either 5 g (P=.0178) or 10 g (P=.0018) vs. placebo.
Similar results were observed among patients with HF who were also receiving RAAS inhibitors. This assessment included 18 treated patients and 22 placebo recipients in the 5-g arm, and 20 treated patients and 20 placebo recipients in the 10-g arm. Patients assigned 5 g (P=.0091) and 10 g (P=.0023) had significantly lower serum potassium levels at 12 days compared with those assigned placebo.
The researchers observed a low incidence of adverse events across all groups, with no significant difference between patients assigned placebo or ZS-9. No deaths occurred during the study period.
“ZS-9 led to a rapid, sustained, dose-dependent reduction in serum potassium,” El-Shahawy, from the Academic Medical Research Institute in Los Angeles, said during a presentation. “The safety profile of ZS-9 was comparable to placebo, with no cases of significant hypokalemia. Maintaining normokalemia may also allow for less dietary restrictions, with improvement in quality of life for many of our patients.”
El-Shahawy told Cardiology Today that a long-term study, assessing ZS-9 treatment durations of 1 month and 3 months, is currently underway, along with another study that will continue the therapy for 1 year.
“Long-term experience with ZS-9 may allow the clinician to continue RAAS blockade, with its proven class 1A indications, in some target populations, vis-à-vis delaying the progression of chronic kidney disease, and improved survival in patients with HF,” he said. – by Adam Taliercio
For more information:
El-Shahawy MA. Late-Breaking Clinical Trials. Presented at: the Heart Failure Society of America Annual Scientific Meeting; Sept. 14-17, 2014; Las Vegas.
Disclosure: El-Shahawy reports serving on advisory boards for and receiving research grants from ZS Pharma.