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

NCT06365684 | Recruiting Phase 4 DMC

• 2 other identifiers: 1335482023-507823-52
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Keywords

Fruit, vegetables and nuts; increase dietary potassium intake; Lokelma; Sodium zirconium Cyclosilicate; Chronic Kidney disease; Safety

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Ambulatory blood pressure (average systolic and diastolic blood pressure over 24 hours)

  6 weeks

• 24 hours albuminuria

  6 weeks

• urinary potassium (mmol/l)

  6 weeks

• Plasma bicarbonate

  6 weeks

• Quality of life, using SF36 questionnaire

  6 weeks

Study Arms (2)

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)

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

Interventions

Sodium zirconium cyclosilicate DRUG

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.

Also known as: Lokelma

Potassium enriched diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic Kidney disease, stage 3 to 4b (eGFR 44-15 ml/min/1.73m\^2)
• Use of inhibitor of the renin-angiotensin system

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• AstraZeneca: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Hyperkalemia; Renal Insufficiency, Chronic

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Joris I Rotmans, Professor

CONTACT

+31 71 5292148; j.i.rotmans@lumc.nl

Wouter T Moest, MD

CONTACT

+31 71 5292148; w.t.moest@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single center, cross-over randomized clinical trial with non-inferiority design

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 15, 2024
• Study Start: April 29, 2024
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: March 6, 2025

Record last verified: 2024-04

Locations

NL (1)