Potassium trap compound restored, maintained levels in HF patients in phase 3 trials

NEW ORLEANS — The selective potassium trap sodium zirconium cyclosilicate effectively restored and maintained normal levels of serum potassium in patients with HF taking renin-angiotensin-aldosterone system inhibitors, according to findings revealed at the annual AAHFN meeting.

These results, from a multicenter, randomized, double blind, placebo-controlled phase 3 trial, suggest the compound, known as ZS-9 (ZS Pharma Inc.), could allow increased use of renin-angiotensin-aldosterone system inhibitor medications, according to researchers.

Nancy M. Albert

“Among patients with [HF], hyperkalemia, or high potassium levels, may prevent use of evidence-based medication therapies known to improve survival and quality of life, and reduce hospitalization rates,” Nancy M. Albert, PhD, RN, of the Cleveland Clinic Health System, told Healio.com. “ZS-9 has the potential to reduce potassium levels, both acutely and chronically.”

Scientists from the Texas pharmaceutical company and Boston Biostatistics Research Foundation evaluated the compound’s clinical benefit in 753 patients with serum potassium levels between 5 mEq/L and 6.5 mEq/L. The investigators randomly assigned patients to one of four doses of ZS-9 (1.25 g, 2.5 g, 5 g or 10g) or placebo orally three times per day for 48 hours (acute phase).

Researchers then randomly assigned patients with potassium levels between 3.5 mEq/L and 5 mEq/L to the same doses or placebo once per day up until 14 days. Patients who initially received placebo were given either of the lower doses (1.25 or 2.5 mEq/L).

The team focused their findings on data from 216 patients with HF taking renin-angiotensin-aldosterone system inhibitors who continued their therapy.

At 48 hours, mean potassium dropped more from baseline (5.3 mEq/L) among patients treated with 10 g ZS-9 than placebo (4.5 vs. 5.1 mEq/L; P < .05), with 204 (94%) patients entering the maintenance phase.

The team then focused on 40 patients (20 patients who remained on 10 g/day ZS-9 and 20 patients who were switched to placebo) for 12 days (chronic phase). Mean potassium remained stable with ZS-9 (4.5 mEq/L at baseline and end of study) but increased with placebo (from 4.5 to 5.1 mEq/L) (P = .002).

During the acute phase, 11.9% of patients taking 10 g three times per day reported adverse events compared with 10.8% of those taking placebo, according to researchers.

“When potassium level is in the normal range, health care providers will be more likely to prescribe life-saving [HF] medications that previously could not be used,” Albert said.

“Currently, we do not have a daily oral medicine that reduces potassium level.”

Although ZS-9 is not FDA approved for use yet, Albert said the study results were promising and noted that the compound would meet an unmet need. However, more investigation is required.

“Future research is underway in a larger sample of patients with HF and for a longer period of time — 1 year rather than less than 4 weeks,” Albert said. – by Allegra Tiver

Reference:

Albert N, et al. Poster P10. Presented at: American Association of Heart Failure Nurses Annual Meeting; June 25-27, 2015; New Orleans.

Disclosure: Albert reports no relevant financial disclosures.