Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone
Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone
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 an 8-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 (<25 mg daily); receiving a beta-blocker unless
 contraindicated; AND with hyperkalemia (sK+ 5.1-5.9 mEq/L) and an eGFR >/= 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 24 months and eGFR >/= 30 mL/min/1.73m2, or sK+ >/= 4.5 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 8-month double-blind, placebo-controlled,
 randomized withdrawal treatment phase.
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 either:

 -  Have a history of HK (sK+ >5.0 mEq/L) within the prior 24 months and eGFR ≥30
 mL/min/1.73 m2, or

 -  sK+ ≥4.5 mEq/L and eGFR 30 to 60 mL/min/1.73 m2 and/or 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) (stable dose for ≥4
 weeks)

 -  Not on spironolactone or eplerenone, or on low-dose spironolactone (<25 mg daily).

 -  Receiving beta-blocker (stable dose for ≥4 weeks) 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 due to HF

 -  Previous cardiac transplantation or implantation of a ventricular assistance device
 (VAD) or similar device, or transplantation or implantation expected after
 randomisation