Sodium zirconium cyclosilicate (SZC) can correct hyperkalemia and maintain normokalemia in ethnically diverse patients, according to a new study.

As part of the phase 3 HARMONIZE-Global trial (NCT02875834), 267 nondialysis outpatients from 45 sites in Japan, Russia, South Korea, and Taiwan who presented with serum potassium levels of 5.1 mmol/L or higher received oral SZC (10 g thrice daily) for 48 hours. Investigators then randomly assigned the 248 patients who experienced serum potassium correction to 3.5 to 5.0 mmol/L to receive SZC (10 g), SZC (5 g), or placebo for 28 days for maintenance therapy. Most patients had chronic kidney disease (78.3%) or diabetes (64.4%) at baseline, 44.2% had both CKD and diabetes; and 18.7% had heart failure. Three-quarters of all patients were taking renin-angiotensin-aldosterone system inhibitors (RAASi).

During the correction phase, mean serum potassium declined significantly by 1.28 mmol/L within 48 hours compared with baseline, Faiez Zannad, MD, PhD, of the University of Lorraine in Nancy, France, and colleagues reported in ESC Heart Failure. During the maintenance phase, SZC 5 and 10 g once-daily significantly reduced mean serum potassium by 9.6% and 17.7%, respectively, compared with placebo. More patients achieved normokalemia by day 29 with SZC 5 g (58.6%) and 10 g (77.3%) compared with placebo (24.0%), with the greatest number of normokalemic days in the 10 g group.

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SZC produced dose-dependent changes in serum potassium, according to Dr Zannad’s team. The current study was designed to support findings of a previous trial in a global population (JAMA 2014; 312: 2223–2233), and the results coincided, they stated.

The most commonly reported drug-related adverse events were mild to moderate edema and constipation. Patients who received SZC 10 g reported a higher incidence of edema and constipation (15.2% and 9.1%, respectively) than those who received SZC 5 g (5.1% and 1.0%, respectively) or placebo. One edema case was due to renal disease. Five edema events prompted drug discontinuation. Edema subsided in the majority of patients.

Disclosure: This clinical trial was funded by AstraZeneca, the makers of sodium zirconium cyclosilicate (Lokelma®). Please see the original reference for a full list of authors’ disclosures.

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Zannad F, Hsu BG, Maeda Y, et al. Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled: HARMONIZE-Global study. ESC Heart Fail. doi: 10.1002/ehf2.12561