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

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 Overview

• Status: Not yet recruiting
• Conditions: Diet Modification; Chronic Kidney Disease; Hyperkalemia; Sodium Zirconium Cyclosilicate
• Intervention / Treatment: Drug: Sodium zirconium cyclosilicate

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joris I Rotmans, Professor; Phone Number: 011 800-555-5555; Email: j.i.rotmans@lumc.nl
• Study Contact Backup: Name: Wouter T Moest, MD; Phone Number: 800-555-5555; Email: w.t.moest@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potassium enriched diet; 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)	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.; Other Names: Lokelma
No Intervention: Regular diet; Patients with chronic kidney disease stage 3b to 4 will followed for 6 weeks, during their regular diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Ambulatory blood pressure	6 weeks
24 hours albuminuria	6 weeks
urinary potassium and sodium excretion	6 weeks
Plasma bicarbonate	6 weeks
Quality of life, using SF36 questionnaire	6 weeks
Effect on stool (assessed with Bristol Stool Chart)	6 weeks
Difference in serum potassium one week after start of study (SCZ free period)	6 weeks
Per protocol analysis of difference in serum potassium after six week (end of study)	6 weeks
Incidence of severe hyperkalemia (serum potassium above 6.5 mmol/l or above 6.0 with ECG features of hyperkalemia)	6 weeks
Incidence of hyperkalemia (serum potassium above 5.5 mmol/l)	6 weeks
Necessity for treatment of hyperkalemia	6 weeks

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Chronic Kidney disease; Lokelma; Fruit, vegetables and nuts; increase dietary potassium intake; Sodium zirconium Cyclosilicate
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Water-Electrolyte Imbalance; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hyperkalemia
• Other Study ID Numbers: 133548; 2023-507823-52 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No