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

Leiden University Medical Center (LUMC)

Status and phase: Enrolling; Phase 4

Conditions: Chronic Kidney Disease; Hyperkalemia; Sodium Zirconium Cyclosilicate; Diet Modification

Treatments: Drug: Sodium zirconium cyclosilicate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06365684

2023-507823-52 (EudraCT Number)

133548

Details and patient eligibility

About

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

Enrollment: 16 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Potassium enriched diet

Experimental group

Description:

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)

Treatment:

Drug: Sodium zirconium cyclosilicate

Regular diet

No Intervention group

Description:

Patients with chronic kidney disease stage 3b to 4 will followed for 6 weeks, during their regular diet