A Multicenter, Prospective, Non-interventional Cohort Study to Evaluate the Safety and Treatment Pattern of Sodium Zirconium Cyclosilicate for Hyperkalaemia Management in Real World Practice in China

Background/Rationale:

Hyperkalaemia (HK) is a common electrolyte disturbance in clinical practice, defined as serum potassium (sK) beyond the normal range. The cut-off value for HK diagnosis is 5.0 mmol/L in most international guidelines[1, 2]. HK changes potassium ion gradient across the cell membrane and affects the excitability and conductivity of cardiomyocytes, leading to various types of arrhythmias, including ventricular arrhythmia, cardiac arrest and sudden death[3]. In the general population, the prevalence of HK is about 2-3%[4-6]. In an epidemiological survey among outpatients in China, 3.86% of general outpatients experienced HK, and the proportion of patients who experienced HK increased in patients with chronic kidney disease (CKD), heart failure, diabetes and hypertension [7].

Sodium Zirconium Cyclosilicate (SZC) is a non-absorbed, non-polymer inorganic powder with a uniform micropore structure that preferentially captures potassium in exchange for hydrogen and sodium cations. SZC captures potassium throughout the entire gastrointestinal (GI) tract and reduces the concentration of free potassium in the GI lumen, thereby lowering sK levels and increasing faecal potassium excretion to resolve HK[8].

The potassium-lowering effects of SZC have been demonstrated in three randomised, double-blind, placebo-controlled trials in patients with HK [9-11]. In addition, two open-label maintenance studies tested long-term safety of SZC[12, 13]. These five studies included 1,760 patients given doses of SZC; 507 exposed for at least 360 days. In the studies, SZC reduced sK and maintained normal sK levels regardless of the underlying cause of HK, age, sex, race, comorbid disease or concomitant use of renin-angiotensin and aldosterone system inhibitors (RAASi).

As of 21 September 2019, the data cut-off date, approximately 2,580 patients have been cumulatively exposed to SZC in completed and on-going clinical trials. Based on the data available now, oedema-related events (including fluid overload, fluid retention, generalised oedema, hypervolaemia, localised oedema, oedema, oedema peripheral, peripheral swelling) and hypokalemia are common (frequency ≥1/100 to >1/10) adverse reactions reported with SZC.