NCT04676646

Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone

Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate (SZC) for the Management of Hyperkalaemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction and Receiving Spironolactone

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 366 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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).

Detailed description

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 (\<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 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.

Conditions

• Hyperkalaemia
• Heart Failure With Reduced Ejection Fraction

Interventions

Type	Name	Description
DRUG	Sodium zirconium cyclosilicate	Investigational medicinal product
DRUG	Placebo	Placebo comparator
OTHER	Spironolactone	Background intervention. During the run-in phase, spironolactone will be initiated/uptitrated up to a maximum of 50 mg per day. During the randomized withdrawal phase the spironolactone dose at the end of the run-in phase will be maintained.

Timeline

• Start date: 2021-03-08
• Primary completion: 2024-07-15
• Completion: 2024-07-15
• First posted: 2020-12-21
• Last updated: 2025-07-09
• Results posted: 2025-07-09

Locations

89 sites across 8 countries: United States, Brazil, Canada, Czechia, Hungary, Poland, Spain, United Kingdom

Regulatory

• FDA-regulated drug study