A Phase 2 interventional study of Sodium zirconium cyclosilicate and Placebo in Heart Failure and Hyperkalemia, sponsored by Michael Fu. Active, not recruiting at 2 sites in Sweden. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-04.
Sponsored by Michael Fu · Phase 2, Interventional, and Treatment
Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The main reason for this seems to be increased risk of hyperkalemia in individuals on MRA. Theoretically, by limiting the risk of hyperkalemia it could thus be possible to optimize MRA therapy. This is studied in this randomized controlled trial in which it is investigated whethere adding a potassium-binder in combination with MRA treatment prevent hyperkalemia to a greater extent than only using MRA.
The specific aim of this study is to demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with HFrEF.
A multicenter, randomized, placebo-controlled, double-blinded study in Sweden (n=110)
The study consists of 2 phases: 1) open-label run-in within maximum 2 months, where all are treated with SZC to test tolarability, and 2) a 1:1 randomized, double-blinded and placebo-controlled treatment during 6 months.
The open-label phase, in turn, consists of three periods: run-in (1 - 2 weeks), correc-tion (maximum 72 hours) and maintenance (4-7 weeks). In addition, post-randomization phase, all patients will be followed by 3 visits (Follow-Up 1, 2 and 3) at 1, 2 and 4 weeks after End of Study (EOS) / End of Treatment (EOT) (which comes first) for further control of kalium and creatinine levels and documentation of current MRA use incl dose.
Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance reg-imen should be started with 5 g once daily. The dose can be titrated up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium.
Primary Objective:
To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimiz-ing MRA in HFrEF, SZC vs Placebo.
Outcome measure: Whether a patient maintains MRA either at a dose ≥ 25 mg daily (for those without MRA at base-line) or a dose increase by 25 mg daily (for those with MRA ≤ 25 mg daily at baseline) and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.
Target subject population
Stable and symptomatic patients with chronic heart failure and LVEF ≤ 40% despite Guideline-Directed Medical Treatment (ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor, MRA) at the discretion of physician´s judgement AND remaining suboptimal treatment of MRA
Duration of treatment
This study consists of 2 treatment phases: 1) Open-label Run-in, and 2) Randomized, pla-cebo-controlled, double-blinded treatment during 6 months. The Open-label phase, in turn, consists of three periods: up-titration (normally 1 - 2 weeks, or longer in some cases), Cor-rection (maximum up to 72 hours) and Maintenance (4-7 weeks)
Investigational product, dosage and mode of administration Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance regimen should be started with 5 g once daily. The dose can be adjusted up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 110 is above the median of 76 across 4,049 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →This is the only study on the registry with Michael Fu as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Recruiting will take place mainly from specialist care at University hospitals or Province hospitals in Sweden. But some of patients might have simultaneous follow-up at primary care as well.
Each subject should meet all of the inclusion criteria and none of the exclusion criteria for this study. Under no circumstances can there be exceptions to this rule.
Inclusion criteria
For inclusion in the study subjects should fulfil the following criteria:
And one of following:
Current S-K 5.1-5.9 mmol/L or P-K 4.9-5.7 mmol/L
Depending on the S-K status during screening, patients are divided into two groups before treatment initiation /run-in:
Group 2: Patients who are normokalemic (S-K 3.5 - 5.0 mmol/L) during screening but are at a high risk of developing hyperkalemia associated with MRA initiation / increase. Namely, one (or both) of the following:
Note: All S-K related limits in this protocol concern serum measurements. In Sweden it is plasma that is analyzed, which makes 4.8 mmol/l (plasma) equivalent to 5.0 mmol/L(serum)
Exclusion Criteria:
Subjects should not enter the study if any of the following exclusion criteria are ful-filled:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Optimal dose of SZC, which is an approved drug for hyperkalemia in Sweden. The subject is treat with 5 mg daily however it can be reduced to once every second day, or inreased to as much as as 10 mg daily, depending on measured potassium levels. This is combined with a mineralcorticoid receptor antagonist (spironolacton or eplerenon), 25 mg or 50 mg depending on what dose they could tolerate.
Drug: Sodium zirconium cyclosilicate
The subject is treat with placebo drug, 5 mg once daily, however it can be reduced to once every second day, or increased to as much as as 10 mg daily, depending on measured potassium levels. This is combined with the dose of mineralcorticoid receptor antagonist (spironolacton or eplerenon) 25 mg or 50 mg depending on what dose they could tolerate.
Other: Placebo
SZC is an approved drug in Sweden and subsidized for patients with chronic kidney disease in stages 3 to 5, with or without chronic heart failure, for whom treatment with Resonium is not suitable and for patients with chronic heart failure without con-comitant chronic kidney disease
Also known as: Lokelma
Treatment with the same dose of placebo medicine as they would have received had they been treated with the interventional drug (SZC).
Optimization of MRA usage by Sodium Zirconium Cyclosilicate in HFrEF
Outcome Measure: Whether a patient maintains MRA either at a dose ≥ 25 mg daily (for those without MRA at base-line) or a dose increase by 25 mg daily (for those with MRA ≤ 25 mg daily at baseline) and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.
Time frame: 180 days during randomization phase
Maintainance of MRA-dose by Sodium Zirconium Cyclosilicate
Measuring whether a patient is able to maintain at least the same MRA dose at the end of study as at the point of randomization without receiving rescue therapy. SZC vs Placebo
Time frame: 180 days during randomization phase
The impact of MRA-optimization on quality of life by Sodium Zirconium Cyclosilicate
Quality of life is measured by KCCQ (the Kansas City Cardiomyopathy Questionnaire): a change in the clinical summary score ( from 0 to 100) with higher scores indicating fewer symptoms and physical limitations, end of study vs at the point of randomizaiton.
Time frame: 180 days during randomization phase
The impact of MRA-optimization on symptomatic relief by Sodium Zirconium Cyclosilicate
Symptomatic relief is evaluated by a composite of change either in NYHA or Lickert Scale as prespecified below: 1. change in the NYHA functional classifi-cation (I-IV) with higher class indicating more symptomatic and physical limita-tions, or 2. change in the 5-point Likert scale (5PLS) with higher score indicating the worst possible shortness of breath
Time frame: 180 days during randomization
The safety of Sodium Zirconium Cyclosilicate
The difference in safety between two groups is assessed by percent of occurrence of any following prespecified safety endpoints (during the randomization phase): 1. Patient with S-K \<3.0 mmol/l (yes/no) 2. Patient with S-K ≥6.0 mmol/l (yes/no) 3. Patient in need of rescue therapy be-cause of hyperkalemia (yes/no) 4. Patient with fluid retention (general edema, peripheral edema, unrelated to heart failure) (yes/no) 5. Patient with gastrointestinal events such as constipation, diarrhea, abdominal pain, nausea or vomiting) (yes/no) 6. Patient with any AE, SAE or DAE (yes/no)
Time frame: 180 days during randomization phase
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data with approved ethical permission. All requests will be evaluated but this does not mean all requests will be shared.
Supporting information: Study protocol, Informed consent form
Time frame: We will share the study protocol once a manuscript relating to results of the trial is published in a peer-reviewed medical journal.
Access criteria: Researchers that ask for access to the study information, were the intention is to evaluate the study and were the anonymity of the study participants is not jeopardized will all be considered for access.
No publications or documents are linked to this record.
Started Sep 2021 (actual). Primary completion is estimated for Dec 2025, 51 months after the start.
Of 111 non-industry phase 2 interventional studies under Heart Failure, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 66. This study's planned 51 months is above that.
Counting every sponsor, half of 184 studies reached it within 29 months; a quarter within 17 and three quarters within 47.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sodium zirconium cyclosilicate