study to assess efficacy and safety of szc for the management of high potassium in patients with symptomatic hfref receiving spironolactone

Conditions: Hyperkalaemia; Heart Failure With Reduced Ejection Fraction

Summary: the main objective of this study is to evaluate the efficacy of szc as compared with placebo in keeping potassium levels within the normal range (3.5-5.0 meq/l) while on spironolactone ≥25 mg daily without assistance of rescue therapy for hyperkalaemia (hk).

realize-k is a phase 4, multinational, multicenter, double-blind, placebo-controlled, randomized-withdrawal, parallel-group study that includes the following 3 phases: screening, 4-6 week open-label run-in phase where sodium zirconium cyclosilicate (szc) and spironolactone will be optimized, followed by a 6-month double-blind, placebo-controlled, randomized withdrawal treatment phase. patients meeting the following criteria will enter the 4-6 week open-label run-in phase: symptomatic heart failure with reduced ejection fraction (hfref); receiving an angiotensin-converting enzyme inhibitor (acei), angiotensin ii receptor blocker (arb), or angiotensin receptor-neprilysin inhibitor (arni); receiving no spironolactone or eplerenone, or receiving low-dose spironolactone (\ /= 30 ml/min/1.73m2, or normokalemic (sk+ 3.5-5.0 meq/l) and 'at risk' of developing hyperkalemia (ie, history of hyperkalemia within the past 36 months and egfr \>/= 30 ml/min/1.73m2, or sk+ 4.5-5.0 meq/l and egfr 30-60 ml/min/1.73m2 and/or age \>75 years). patients who are normokalemic on szc and receiving spironolactone \>/= 25 mg daily at the end of the open-label run-in phase will enter the 6-month double-blind, placebo-controlled, randomized withdrawal treatment phase. eligible patients will be randomized 1:1, stratified by run-in phase sk+ cohort.

Eligibility criteria:
inclusion criteria * adults aged ≥18 years * potassium and estimated glomerular filtration rate (egfr): * cohort 1: sk+ 5.1-5.9 meq/l at screening/study enrolment and egfr ≥30 ml/min/1.73 m2; or * cohort 2: normokalaemic (sk+ 3.5-5.0 meq/l) at screening and 'at risk' of developing hk defined as any of the following: * have a history of hk (sk+ \>5.0 meq/l) within the prior 36 months and egfr ≥30 ml/min/1.73 m2; or * sk+ 4.5-5.0 meq/l and egfr 30 to 60 ml/min/1.73 m2; or * sk+ 4.5-5.0 meq/l, and age \>75 years * symptomatic hfref (new york heart association \[nyha\] class ii-iv), which has been present for at least 3 months * left ventricular ejection fraction (lvef) ≤40% * receiving angiotensin-converting enzyme inhibitor (acei), angiotensin ii receptor blocker (arb), or angiotensin receptor-neprilysin inhibitor (arni) * not on or on low-dose spironolactone or eplerenone (\<25 mg daily) * receiving beta-blocker unless contraindicated exclusion criteria * heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or severe stenotic valve disease as a primary cause of hf * current inpatient hospitalisation with unstable hf, defined as any of the following: * systolic blood pressure \<95 mmhg during the 6 hours prior to screening. * intravenous diuretic therapy during the 12 hours prior to screening. * use of intravenous inotropic drugs during the 24 hours prior to screening. * received mechanical circulatory support during the 48 hours prior to screening * previous cardiac transplantation or implantation of a ventricular assistance device (vad) or similar device, or transplantation or implantation expected after randomisation