Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4

Chronic Kidney Disease Clinical Trial

— LIBRAL  

Official title:

Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06365684
• Other study ID #: 133548
• Secondary ID: 2023-507823-52
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 29, 2024
• Est. completion date: May 1, 2025

Study information

• Verified date: April 2024
• Source: Leiden University Medical Center
• Contact: Joris I Rotmans, Professor
• Phone: 800-555-5555
• Email: j.i.rotmans[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic Kidney disease, stage 3 to 4b (eGFR 44-15 ml/min/1.73m^2)

• Use of inhibitor of the renin-angiotensin system

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diet Modification
• Hyperkalemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Sodium zirconium cyclosilicate
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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 weeks
Secondary	Ambulatory blood pressure (average systolic and diastolic blood pressure over 24 hours)		6 weeks
Secondary	24 hours albuminuria		6 weeks
Secondary	urinary potassium (mmol/l)		6 weeks
Secondary	Plasma bicarbonate		6 weeks
Secondary	Quality of life, using SF36 questionnaire	36-Item Short Form Survey. Scoring can range from 0 to 100. Higher scores indicate better health status	6 weeks
Secondary	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.	6 weeks
Secondary	Difference in serum potassium one week after start of study (SCZ free period)		6 weeks
Secondary	Per protocol analysis of difference in serum potassium after six week (end of study)		6 weeks
Secondary	Incidence of severe hyperkalemia (serum potassium above 6.5 mmol/l or above 6.0 with ECG features of hyperkalemia)		6 weeks
Secondary	Incidence of hyperkalemia (serum potassium above 5.5 mmol/l)		6 weeks
Secondary	Necessity for treatment of hyperkalemia		6 weeks
Secondary	urinary sodium (mmol/l)		6 weeks