Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone (REALIZE-K)
Hyperkalaemia, Heart Failure With Reduced Ejection Fraction
About this trial
This is an interventional treatment trial for Hyperkalaemia
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 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
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Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Open-label run-in phase
Randomized withdrawal phase (6 months)
Cohort 1 (4 weeks duration): Patients who are hyperkalemic at study entry will begin SZC 10 g TID for up to 48 hours followed by SZC 10 g once daily to achieve and maintain normokalemia. The SZC dose will be adjusted as needed to maintain normokalemia (dose range = 5 g every other day, to 5-15 g once daily). Cohort 2 (up to 6 weeks duration): Patients who develop hyperkalemia during the uptitration of spironolactone will receive SZC 10 g TID for up to 48 hours followed by SZC 10 g once daily to achieve and maintain normokalemia. The SZC dose will be adjusted as needed to maintain normokalemia (dose range = 5 g every other day, to 5-15 g once daily).
SZC arm and Placebo arm: Patients will continue on the SZC dose they were receiving at the end of the run-in phase. The SZC / Placebo dose will be adjusted as needed to maintain normokalemia (dose range = 5 g every other day, to 5-15 g once daily).