Phase 4
Completed N=366
Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone
Hyperkalaemia · Heart Failure with Reduced Ejection Fraction
Source: ClinicalTrials.gov NCT04676646 ↗
Enrolled (actual)
366
Serious AEs
9.9%
Results posted
Jul 2025
Primary outcomePrimary: Participants Who Achieved Response, Defined as Serum Potassium (sK+) Within 3.5 to 5.0 mEq/L, Spironolactone Greater Than or Equal to 25 mg Daily, no Rescue Therapy for Hyperkalaemia — 72.1; 35.7 Percentage of participants — p=<0.001
◆ Published Evidence
Established
44citations · ~44 / year
Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure.
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).
Linked Publications (2)
-
Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure.
-
Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia: REALIZE-K Design and Baseline Characteristics.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Participants Who Achieved Response, Defined as Serum Potassium (sK+) Within 3.5 to 5.0 mEq/L, Spironolactone Greater Than or Equal to 25 mg Daily, no Rescue Therapy for Hyperkalaemia |
72.1; 35.7 | <0.001 sig |
| SECONDARY Participants Who Achieved Response, Defined as sK+ Within 3.5-5.0 mEq/L, on the Same Dose of Spironolactone as Randomisation, no Rescue Therapy for Hyperkalaemia |
58.2; 22.9 | <0.001 sig |
| SECONDARY Participants Who Achieved Response, Defined as Spironolactone Greater Than or Equal to 25 mg Daily |
81.4; 49.5 | <0.001 sig |
| SECONDARY Time to First Hyperkalaemia (sK+ Greater Than 5.0mEq/L) Episode |
65.0; 9.0 | <0.001 sig |
| SECONDARY Time to First Instance of Decrease or Discontinuation of Spironolactone Dose Due to Hyperkalaemia |
NA; NA | 0.006 sig |
| SECONDARY Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at EOT |
71.27; 72.27 | 0.724 |
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
Data sourced from ClinicalTrials.gov (NCT04676646) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.