Phase 4 N=366 Randomized Double-blind Treatment

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

Bottom Line

View on ClinicalTrials.gov: NCT04676646 ↗

Enrolled (actual)

366

Serious AEs

9.9%

Results posted

Jul 2025

Primary outcome: 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 Percentage of participants — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Sodium zirconium cyclosilicate (Drug); Placebo (Drug); Spironolactone (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: AstraZeneca
Primary completion: Jul 2024

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

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).

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04676646). 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.