What side effects are associated with this type of intervention?

Common treatments for heart failure, including potassium binders like Sodium Zirconium Cyclosilicate (SZC) and patiromer, often cause gastrointestinal side effects such as constipation, diarrhea, and nausea. Other heart failure medications, such as ACE inhibitors, beta-blockers, and diuretics, have their own side effects. ACE inhibitors may cause cough, elevated potassium levels, and kidney dysfunction. Beta-blockers can lead to fatigue, dizziness, and slow heart rate, while diuretics may result in electrolyte imbalances, dehydration, and kidney issues.

What prior FDA approvals exist?

The FDA has approved several treatments for heart failure, including medications that manage hyperkalemia, a common complication in these patients. Sodium Zirconium Cyclosilicate (SZC) is a potassium binder that helps to lower serum potassium levels, particularly in patients receiving medications like spironolactone. Other FDA-approved potassium binders include patiromer (Veltassa), which also treats hyperkalemia in heart failure patients. Additionally, heart failure management often involves the use of ACE inhibitors, beta-blockers, and diuretics, which help to improve heart function and manage symptoms.

What other types of research exist?

Promising novel alternatives to SZC for managing high potassium levels in heart failure patients include patiromer, which is another potassium binder that has shown efficacy in lowering serum potassium levels. Additionally, newer agents such as Lokelma (another name for SZC) and potential advancements in gene therapy or novel diuretics targeting potassium regulation may also be considered. It is important to consult with a healthcare provider to determine the most appropriate treatment based on individual patient needs and the latest clinical evidence.

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Electrolyte Modifying Agent

SZC for High Potassium in Heart Failure Patients (REALIZE-K Trial)

Phase 4

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Receiving angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor blocker (ARB), or angiotensin receptor-Neprilysin inhibitor (ARNi)

Cohort 1: sK+ 5.1-5.9 mEq/L at screening/study enrolment and eGFR ≥30 mL/min/1.73 m2; OR

Must not have

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:

Timeline

Screening 3 weeks

Treatment Varies

Follow Up the monthly visits are used for response assessment from month 1 to month 6

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial tests if SZC can keep potassium levels normal in heart failure patients taking spironolactone. SZC acts like a sponge to soak up extra potassium and remove it from the body. SZC is a newly introduced treatment that effectively lowers and maintains normal potassium levels in patients with high potassium.

Who is the study for?

Adults over 18 with heart failure and high potassium levels, taking specific heart medications, can join this trial. They must have a stable blood pressure and not be hospitalized for unstable heart conditions or on certain intravenous drugs.

What is being tested?

The study tests if SZC keeps potassium levels normal in patients with symptomatic HFrEF who are also taking spironolactone. Participants will either receive SZC or a placebo to compare effectiveness without rescue therapy.

What are the potential side effects?

While the side effects of SZC aren't detailed here, common ones may include nausea, vomiting, constipation, and swelling. Spironolactone can cause kidney problems, high potassium levels, dizziness, rash.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am taking medication for my blood pressure or heart condition.

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My blood potassium is between 5.1-5.9 and my kidney function is good.

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My potassium levels are between 4.5 and 5.0, and I am over 75 years old.

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My potassium levels are between 4.5-5.0 and my kidney function is moderately reduced.

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I am not taking or only taking a low dose of spironolactone or eplerenone.

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I have had high potassium levels and my kidney function is okay.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart failure is caused by a specific heart condition.

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I am currently hospitalized with unstable heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ the monthly visits are used for response assessment from month 1 to month 6

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~the monthly visits are used for response assessment from month 1 to month 6

This trial's timeline: 3 weeks for screening, Varies for treatment, and the monthly visits are used for response assessment from month 1 to month 6 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Response is defined by Having(sK+) within 3.5-5.0 mEq/L AND Being on spironolactone ≥25 mg daily AND Not using rescue therapy for HK during the last month. The treatment effect concerns the overall

Secondary study objectives

Change in KCCQ-CSS at EOT visit (approximately 6 months post-randomisation) from randomisation. SZC compared with placebo using difference in mean

Per visit, response is defined by Having potassium (sK+) within 3.5-5.0 mEq/L as assessed by central laboratory AND Being on the same spironolactone dose as they were at randomisation AND Not using rescue therapy for HK during the last month

Response is defined by Being on spironolactone ≥25 mg daily The treatment effect concerns the overall

+2 more

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Randomized withdrawal phase (6 months)Experimental Treatment3 Interventions

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).

Group II: Open-label run-in phaseExperimental Treatment3 Interventions

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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sodium zirconium cyclosilicate

2021

Completed Phase 4

~690

Placebo

1995

Completed Phase 3

~2670

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for heart failure include aldosterone antagonists like spironolactone, which help reduce fluid retention and prevent cardiac remodeling but can increase serum potassium levels. Potassium binders like Sodium Zirconium Cyclosilicate (SZC) are used to manage hyperkalemia by binding potassium in the gastrointestinal tract, thus lowering serum potassium levels. ACE inhibitors and beta-blockers are also frequently used; ACE inhibitors reduce blood pressure and decrease the workload on the heart by inhibiting the conversion of angiotensin I to angiotensin II, while beta-blockers slow the heart rate and reduce myocardial oxygen demand. These treatments are crucial for heart failure patients as they help manage symptoms, prevent disease progression, and reduce the risk of complications such as hyperkalemia and sudden cardiac death.

The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig.New angiotensin II type 1 receptor blocker, azilsartan, attenuates cardiac remodeling after myocardial infarction.Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.