Publication Date

6-1-2020

Journal

Academic Emergency Medicine

DOI

10.1111/acem.13954

PMID

32149451

PMCID

PMC7318712

PubMedCentral® Posted Date

3-28-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adult, Diabetes Mellitus, Double-Blind Method, Emergency Treatment, Female, Humans, Hyperkalemia, Insulin, Male, Middle Aged, Pilot Projects, Potassium, Renin-Angiotensin System, Silicates, Treatment Outcome

Abstract

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+) from baseline until 4 hours after start of dosing.

RESULTS: Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was –0.41 (±0.11) mmol/L and –0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = –0.13 mmol/L, 95% confidence interval [CI] = –0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: –0.72 (±0.12) versus –0.36 (±0.11) mmol/L (LSM difference = –0.35 mmol/L, 95% CI = –0.68 to –0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium‐lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours.

CONCLUSIONS: This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.

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