HyperkalemiaPhase 4LIBRALNCT06365684
Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4
A Phase 4 study testing Sodium zirconium cyclosilicate in people with Hyperkalemia and Diet Modification, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Several studies have shown that higher urinary potassium excretion (as proxy for potassium intake) is associated with better kidney outcomes, lower blood pressure and improved survival. These associations are also observed in patients with (advanced) CKD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperkalemia, Diet Modification, Chronic Kidney Disease
- What is being tested?
- Sodium zirconium cyclosilicate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- 29 Apr 2024to 1 May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic Kidney disease, stage 3 to 4b (eGFR 44-15 ml/min/1.73m^2)
- Use of inhibitor of the renin-angiotensin system
Who cannot join
- Hyperkaliemia (plasma potassium \> 5.5 mmol/L) at baseline or at the start of potassium enriched diet
- Use of potassium binders at baseline or at the start of potassium enriched diet
- Use of dual RAAS-blockade, mineralocorticoid receptor blockers or potassium-sparing diuretics
- Use of calcineurin inhibitors
- Use of trimethoprim and sulfamethoxazole
- Patients with a previous history of ventricular cardiac arrhythmia
Show all 12Show fewer
- Patients with a prolonged QTc time on ECG
- Kidney transplantation patients
- Patients with a life expectancy of \< 6 months
- Incapacitated subjects or subjects who are deemed unfit to adequately adhere to instructions from the research team
- Women who are pregnant, breastfeeding or considering pregnancy in the coming 6 months.
- Hypersensitivity to SCZ
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
Joris I. Rotmans, professor, +31 71 5262148, j.i.rotmans@lumc.nl
Wouter Moest, MD, +31 71 5262148, w.t.moest@lumc.nl
About this study
Rationale: Several studies have shown that higher urinary potassium excretion (as proxy for potassium intake) is associated with better kidney outcomes, lower blood pressure and improved survival. These associations are also observed in patients with (advanced) CKD. However, application in daily practice in patients with CKD, is impaired by the risk of hyperkalemia, due to metabolic acidosis and impaired renal potassium excretion in these patients. As a consequence, patients with CKD are advised to restrict their intake of fruit and vegetables, as these healthy food components are important sources of dietary potassium. This is particularly undesirable for patients with CKD in view of the very high risk of cardiovascular disease.
Concomitant use of sodium zirconium cyclosilicate (SZC) could allow a more liberal intake of fruit and vegetables for patients with CKD, as SZC effectively treats hyperkalemia and counteracts metabolic acidosis [1]. With this strategy, the beneficial effects of potassium in fruits and vegetables on (vascular) health could also become accessible to patients with CKD.
Read more
Objective: To demonstrate that a potassium-rich diet, including the use of SZC as potential rescue treatment (in case of hyperkalemia), does not result in an unacceptable rise in plasma potassium (i.e. max rise of 0.5 mmol/L and no hyperkalemia). Study Design: Investigator initiated, single center, cross-over randomized clinical trial with non-inferiority design (14 weeks, 2 groups: regular diets vs. diet with potassium rich fruits and vegetables with sodium zirconium cyclosilicate if necessary) Study population: Outpatients ( age ≥ 18 years ) with chronic kidney disease stage IIIb/IV and use of inhibitor of the renin-angiotensin system (RASi).
Intervention: Addition of fruit- and vegetables that contain 40 mmol of potassium on top of regular diet. Addition of SZC after 1 week in case hyperkaliemia develops (serum potassium \> 5,5 mmol/L). Weekly measurement of plasma potassium and dose adjustment of SZC if needed
- Being tested
- Sodium zirconium cyclosilicate
- Keywords
- Fruit, vegetables and nuts, increase dietary potassium intake, Lokelma, Sodium zirconium Cyclosilicate, Chronic Kidney disease, Safety
- Medical subject headings
- Hyperkalemia, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium zirconium cyclosilicateDrug
Also called Lokelma
In the case of hyperkalemia patients will be treated with Sodium zirconium cyclosilicate to allow the continuation of potassium enriched diet. In case hyperkalemia arises in the control group, patients will be treated with Sodium zirconium cyclosilicate as well.
| Study group | Role | What they receive |
|---|---|---|
| Potassium enriched diet | Experimental | Patients with chronic kidney disease stage 3b to 4 will be treated for 6 weeks with a potassium enriched diet (adding +40mmol/day in the form of fruits/vegetables/nuts) Receives: Drug: Sodium zirconium cyclosilicate |
| Regular diet | No intervention | Patients with chronic kidney disease stage 3b to 4 will followed for 6 weeks, during their regular diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference of serum potassium at baseline and after six weeks of treatment with potassium enriched diet (non-inferiority design) compared to the control group. With an intention to treat analysis.
Measured: 6 weeks
Secondary outcomes (12)
Ambulatory blood pressure (average systolic and diastolic blood pressure over 24 hours)
Measured: 6 weeks
24 hours albuminuria
Measured: 6 weeks
urinary potassium (mmol/l)
Measured: 6 weeks
Plasma bicarbonate
Measured: 6 weeks
Quality of life, using SF36 questionnaire
36-Item Short Form Survey. Scoring can range from 0 to 100. Higher scores indicate better health status
Measured: 6 weeks
Effect on stool (assessed with Bristol Stool Chart)
Scoring can range form 1 to 7. Where score of 1 indicates obstipation, score of 4 indicates normal defecation and 7 indicates watery defecation.
Measured: 6 weeks
Difference in serum potassium one week after start of study (SCZ free period)
Measured: 6 weeks
Per protocol analysis of difference in serum potassium after six week (end of study)
Measured: 6 weeks
Incidence of severe hyperkalemia (serum potassium above 6.5 mmol/l or above 6.0 with ECG features of hyperkalemia)
Measured: 6 weeks
Incidence of hyperkalemia (serum potassium above 5.5 mmol/l)
Measured: 6 weeks
Necessity for treatment of hyperkalemia
Measured: 6 weeks
urinary sodium (mmol/l)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2024
- Study start29 Apr 2024
- Primary completion1 May 2025 (estimated)
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperkalemiaStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single center, cross-over randomized clinical trial with non-inferiority design
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, JorisRotmans, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06365684
- Sponsor's protocol ID
- 133548
- Other IDs
- 2023-507823-52, 2023
- Acronym
- LIBRAL
- Status last verified
- Apr 2024
- First submitted
- 10 Apr 2024
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4
- ClinicalTrials.gov ID
- NCT06365684
- Acronym / sponsor ID
- LIBRAL / 133548
- Keywords
- Fruit, vegetables and nuts, increase dietary potassium intake, Lokelma, Sodium zirconium Cyclosilicate, Chronic Kidney disease, Safety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 29 Apr 2024 (actual)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 15 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Several studies have shown that higher urinary potassium excretion (as proxy for potassium intake) is associated with better kidney outcomes, lower blood pressure and improved survival. These associations are also observed in patients with (advanced) CKD. However, application in daily practice in patients with CKD, is impaired by the risk of hyperkalemia, due to metabolic acidosis and impaired renal potassium excretion in these patients. As a consequence, patients with CKD are advised to restrict their intake of fruit and vegetables, as these healthy food components are important sources of dietary potassium. This is particularly undesirable for patients with CKD in view of the very high risk of cardiovascular disease.
Concomitant use of sodium zirconium cyclosilicate (SZC) could allow a more liberal intake of fruit and vegetables for patients with CKD, as SZC effectively treats hyperkalemia and counteracts metabolic acidosis [1]. With this strategy, the beneficial effects of potassium in fruits and vegetables on (vascular) health could also become accessible to patients with CKD.
Objective: To demonstrate that a potassium-rich diet, including the use of SZC as potential rescue treatment (in case of hyperkalemia), does not result in an unacceptable rise in plasma potassium (i.e. max rise of 0.5 mmol/L and no hyperkalemia). Study Design: Investigator initiated, single center, cross-over randomized clinical trial with non-inferiority design (14 weeks, 2 groups: regular diets vs. diet with potassium rich fruits and vegetables with sodium zirconium cyclosilicate if necessary) Study population: Outpatients ( age ≥ 18 years ) with chronic kidney disease stage IIIb/IV and use of inhibitor of the renin-angiotensin system (RASi).
Intervention: Addition of fruit- and vegetables that contain 40 mmol of potassium on top of regular diet. Addition of SZC after 1 week in case hyperkaliemia develops (serum potassium \> 5,5 mmol/L). Weekly measurement of plasma potassium and dose adjustment of SZC if needed
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single center, cross-over randomized clinical trial with non-inferiority design
| Arm | Type | Receives |
|---|---|---|
| Potassium enriched diet | Experimental | Drug: Sodium zirconium cyclosilicatePatients with chronic kidney disease stage 3b to 4 will be treated for 6 weeks with a potassium enriched diet (adding +40mmol/day in the form of fruits/vegetables/nuts) |
| Regular diet | No intervention | –Patients with chronic kidney disease stage 3b to 4 will followed for 6 weeks, during their regular diet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Chronic Kidney disease, stage 3 to 4b (eGFR 44-15 ml/min/1.73m^2)
- Use of inhibitor of the renin-angiotensin system
Key exclusion criteria (12 listed)
- Hyperkaliemia (plasma potassium \> 5.5 mmol/L) at baseline or at the start of potassium enriched diet
- Use of potassium binders at baseline or at the start of potassium enriched diet
- Use of dual RAAS-blockade, mineralocorticoid receptor blockers or potassium-sparing diuretics
- Use of calcineurin inhibitors
- Use of trimethoprim and sulfamethoxazole
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium zirconium cyclosilicateAlso: LokelmaIn the case of hyperkalemia patients will be treated with Sodium zirconium cyclosilicate to allow the continuation of potassium enriched diet. In case hyperkalemia arises in the control group, patients will be treated with Sodium zirconium cyclosilicate as well. | Drug | Potassium enriched diet |
Primary outcome
The difference of serum potassium at baseline and after six weeks of treatment with potassium enriched diet (non-inferiority design) compared to the control group. With an intention to treat analysis.
Time frame: 6 weeks
12 secondary outcomes
Ambulatory blood pressure (average systolic and diastolic blood pressure over 24 hours)
Time frame: 6 weeks
24 hours albuminuria
Time frame: 6 weeks
urinary potassium (mmol/l)
Time frame: 6 weeks
Plasma bicarbonate
Time frame: 6 weeks
Quality of life, using SF36 questionnaire
Time frame: 6 weeks
Effect on stool (assessed with Bristol Stool Chart)
Time frame: 6 weeks
Difference in serum potassium one week after start of study (SCZ free period)
Time frame: 6 weeks
Per protocol analysis of difference in serum potassium after six week (end of study)
Time frame: 6 weeks
Incidence of severe hyperkalemia (serum potassium above 6.5 mmol/l or above 6.0 with ECG features of hyperkalemia)
Time frame: 6 weeks
Incidence of hyperkalemia (serum potassium above 5.5 mmol/l)
Time frame: 6 weeks
Necessity for treatment of hyperkalemia
Time frame: 6 weeks
urinary sodium (mmol/l)
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Hyperkalemia
Enrolling by invitationObservational study
AK+ Guard™ Pilot Study in Chronic Kidney Disease: Outpatient Diagnostic Accuracy and Remote Monitoring
Hyperkalemia, Chronic Kidney Disease (Stage 3-4)
RecruitingPhase 3
A Phase 3 Study Evaluating the Efficacy and Safety of WS016 for the Treatment of Hyperkalemia
Hyperkalemia
Not yet recruiting
Effects of Minimally vs. Ultra-Processed Diets on Potassium (K) Handling in CKD
Chronic Kidney Disease
Enrolling by invitationPhase 4
Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
Chronic Kidney Disease, Type 2 Diabetes
Recruiting
Safety of a Healthy Plant-based Diet With Higher Potassium Content, Compared to a Healthy Plant-based Diet With Limited Potassium Content in Patients With Chronic Kidney Disease: A Pilot Study
Hyperkalemia, Chronic Kidney Disease (Stages 4 and 5)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sodium zirconium cyclosilicate in people with Hyperkalemia and Diet Modification, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joris I Rotmans, Professor (+31 71 5292148, j.i.rotmans@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference of serum potassium at baseline and after six weeks of treatment with potassium enriched diet (non-inferiority design) compared to the control group. With an intention to treat analysis. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.