Título

SODIUM ZIRCONIUM CYCLOSILICATE FOR HYPERKALEMIA: RESULTS OF THE RANDOMIZED, PLACEBO-CONTROLLED, MULTI-DOSE HARMONIZE-GLOBAL STUDY

Introdução

Sodium zirconium cyclosilicate (SZC) is an odorless, tasteless, inorganic, oral, potassium (K) binder approved for the treatment of hyperkalemia in adults in the US and Europe. In the HARMONIZE trial (Kosiborod, JAMA 2015), SZC rapidly corrected and maintained control for 28 days in Caucasian patients with few dose-related adverse events (AEs). Presented here is the HARMONIZE Global study; a 28-day, multicenter, randomized, double-blind, placebo-controlled phase 3 study that evaluated the efficacy and safety of SZC for hyperkalemia in primarily Asian patients.

Material e Método

Outpatients (≥18 yrs) with K ≥5.1mEq/L (measured by the point-of-care device iSTAT) were enrolled from sites in Japan, South Korea, Russia and Taiwan. During the open-label correction phase (CP), patients received SZC 10 g thrice daily for 48 hours, changes in serum K (sK) were evaluated serially. Patients with K 3.5–5.0 mEq/L in the CP entered the 28-day maintenance phase (MP) and were randomized 2:2:1 to receive 5 g SZC, 10 g SZC, or placebo once daily. Background renin angiotensin aldosterone system inhibitors and diuretic use were kept stable. The primary endpoint was the mean serum K (measured by central laboratory) during days 8–29 in MP. Secondary endpoints included changes in sK, proportion of patients who achieved normokalemia (sK 3.5–5.0 mEq/L) in CP and those who maintained normokalemia in MP, quality of life (assessed using EuroQol-5D questionnaire), and changes in aldosterone and renin. Safety parameters included adverse events, vital signs, ECG, and clinical laboratory evaluations.

Resultados

Efficacy and safety data will be available for presentation.

Discussão e Conclusões

A randomized, controlled trial of two doses of SZC for hyperkalemia versus placebo was conducted over 28 days in a population of primarily Asian patients; the results will be important for the use of this potassium binder in this population.

Palavras Chave

Hyperkalemia; Potassium binder; Sodium Zirconium Cyclosilicate