Clinical trial NCT06365684: Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4
Official title: Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2024-04-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single center, cross-over randomized clinical trial with non-inferiority design
Primary purpose: TREATMENT

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 \&gt; 5,5 mmol/L). Weekly measurement of plasma potassium and dose adjustment of SZC if needed


Eligibility criteria: 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 \&gt; 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 \&lt; 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

Primary outcomes:
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.
timeFrame: 6 weeks
Secondary outcomes:
measure: Ambulatory blood pressure (average systolic and diastolic blood pressure over 24 hours)
timeFrame: 6 weeks
measure: 24 hours albuminuria
timeFrame: 6 weeks
measure: urinary potassium (mmol/l)
timeFrame: 6 weeks
measure: Plasma bicarbonate
timeFrame: 6 weeks
measure: Quality of life, using SF36 questionnaire
timeFrame: 6 weeks
measure: Effect on stool (assessed with Bristol Stool Chart)
timeFrame: 6 weeks
measure: Difference in serum potassium one week after start of study (SCZ free period)
timeFrame: 6 weeks
measure: Per protocol analysis of difference in serum potassium after six week (end of study)
timeFrame: 6 weeks
measure: Incidence of severe hyperkalemia (serum potassium above 6.5 mmol/l or above 6.0 with ECG features of hyperkalemia)
timeFrame: 6 weeks
measure: Incidence of hyperkalemia (serum potassium above 5.5 mmol/l)
timeFrame: 6 weeks
measure: Necessity for treatment of hyperkalemia
timeFrame: 6 weeks
measure: urinary sodium (mmol/l)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South-Holland
Study officials:
References: