Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥ 5.5 mmol/L: pooled analysis from two phase 3 trials

BMC Nephrol. 2019 Dec 2;20(1):440. doi: 10.1186/s12882-019-1611-8.

Abstract

Background: Reliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.

Methods: Data were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.

Results: At baseline, 125 of 170 patients (73.5%) had potassium level 5.5-< 6.0, 39 (22.9%) had potassium level 6.0-6.5, and 6 (3.5%) had potassium level > 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1-2.0) and 21.6 (4.1-22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.

Conclusions: SZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.

Trial registration: ClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.

Keywords: Efficacy; Hyperkalemia; Safety; Sodium zirconium cyclosilicate.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Double-Blind Method
  • Drug Monitoring / methods
  • Drug Monitoring / statistics & numerical data
  • Female
  • Humans
  • Hyperkalemia* / blood
  • Hyperkalemia* / drug therapy
  • Ion Exchange Resins / administration & dosage
  • Ion Exchange Resins / adverse effects
  • Male
  • Middle Aged
  • Potassium / blood
  • Silicates* / administration & dosage
  • Silicates* / adverse effects
  • Treatment Outcome

Substances

  • Ion Exchange Resins
  • Silicates
  • sodium zirconium cyclosilicate
  • Potassium

Associated data

  • ClinicalTrials.gov/NCT01737697
  • ClinicalTrials.gov/NCT02088073