A Phase 3 interventional study of Sodium Zirconium Cyclosilicate in Chronic Kidney Diseases, sponsored by Fundación para la Investigación del Hospital Clínico de Valencia. Recruiting at 5 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-09.
Sponsored by Fundación para la Investigación del Hospital Clínico de Valencia · Phase 3, Interventional, and Treatment
Phase III, multicenter, randomized, open-label, parallel-group, non-inferiority, phase III clinical trial comparing CSZ (Lokelma) vs. iSRAA discontinuation/reduction and/or ARM (standard treatment).
Hyperkalemia is a potentially life-threatening condition associated with ventricular arrhythmias and sudden cardiac arrest. It is common in patients with some comorbidities such as chronic kidney disease, congestive heart failure, cardiovascular disease, diabetes or liver disease. Most of these patients should receive drugs that block the renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRA), that increase the risk of hyperkalemia.
For these reasons, relatively few patients receive maximum doses of RAASi / MRA. The dose and its usage decline following an hyperkalemia episode. However, RAASi / MRA discontinuation because of hyperkalemia, represents an undesirable clinical scenario, loosing their potential cardiorenal and nephroprotective benefit. Patients on submaximum doses or who discontinued RAASi / MRA have worse outcomes than patients on maximum doses.
In this study 78 adult patients will be randomized to one of two treatment arms to analyze the proportion of patients achieving sK of \< 5.5 mEq/L:
The study will be conducted in 3 periods:
All the patients randomized and completing the treatment assigned will be participating in the study for an stimated period of 90 ± 13 d. The clinical trial will be finalized when the last 90-day follow-up of the last patient included is performed.
Exclusion Criteria:
Patients assigned to this group will have their iSRAA and/or ARM treatment withdrawn or reduced, according to standard clinical practice.
Patients assigned to this group will be maintained on treatment with iSRAA and/or ARM and oral treatment with CSZ (Lokelma) will be added. A single dose of CSZ consists of one to three sachets (5 to 10 g of active ingredient per sachet) that the subject must suspend in 45 mL of water.
Drug: Sodium Zirconium Cyclosilicate
The recommended starting dose of Lokelma is 10 g, administered three times a day. If, at any time during the study, sK is \> 6.5 mEq/L, treatment for acute hyperkalemia will be started following common clinical practice and local protocols, and investigator will consider RAASi / MRA withdrawal, or downtitration. In this case (confirmed sK \> 6.5 mEq/L despite the maximum SZC dose) patient will leave the IP and will be counted as a treatment failure. If sK is ≤ 3.0 mEq/L, discontinue SZC. The subject should immediately receive appropriate medical intervention. If sK is between 3.1-5.1 mEq/L, pause SZC and re-evaluate in a week. This one-week SCZ treatment temporary discontinuation can only be applied once; if a new sK value between 3.1-5.1 mEq/L is detected, patient will leave the IP permanently. Depending on the serum potassium levels at each visit, the dose of SZC will be adjusted.
Also known as: Lokelma
Percentage of patients achieving serum potassium < 5.5mEq/L at three or all timepoints (7, 30, 60 or 90 days) after follow up (90 days) in both groups.
To analyze the proportion of patients achieving sK of \< 5.5 mEq/L with Sodium zirconium cyclosilicate (SZC) versus discontinuation of RAASi and/or MRA in patients with hyperkalemia and non dialysis CKD.
Time frame: Through study completion, an average of 1 year
Percentage of patients achieving serum potassium < 5 mEq/L at two of the four temporal points in both groups.
To determine if the percentage of patients achieving serum potassium \< 5 mEq/L at two of the four temporal points is not inferior in SZC compared to RAASi / MRA discontinuation or downtitration.
Time frame: Through study completion, an average of 1 year
Number of patients treated with SZC with reduction of serum potassium > 20% after baseline in each time point.
To determine the number of patients treated with SZC who effectively reduce serum potassium \> 20 % over the baseline at days 7, 30, 60 and 90 compared to RAASi / MRA discontinuation or downtitration.
Time frame: Through study completion, an average of 1 year
Percentage of patients achieving serum potassium below 5, 5.5, 6, 6.5 mEq/L in each time point.
To compare percentage of patients achieving serum potassium below 5, 5.5, 6, 6.5 mEq/L at days 7, 30, 60 and 90 in both groups.
Time frame: Through study completion, an average of 1 year
Percentage of patients requiring additional treatments for hyperkalemia in both groups (potassium binding resins, adding or increasing loop diuretics, or discontinuation of RAASi and/or MRA in Lokelma group.
To compare the need for additional treatments for serum hyperkalemia between both groups during the study (potassium binding resins, adding or increasing loop diuretics if hypervolemia).
Time frame: Through study completion, an average of 1 year
Mean change in the urine albumin-to-creatinine ratio (UACR) at 90 days from baseline in patients treated with SZC compared to RAASi / MRA discontinuation or downtitration.
To compare albuminuria changes at 90 days from baseline.
Time frame: Through study completion, an average of 1 year
Mean and standard deviation comparation scores between groups at baseline and at the end of the study (visit 1 and 7) (MLHFQ and SF-36)
To demonstrate an improvement in health-related quality of life in this patient population in patients treated with SZC when compared to the patients non treated with the drug.
Time frame: Through study completion, an average of 1 year
Proportion of patients in each group with downtitration (decrease 25 %, 50 % 75 % or discontinuation of RAASi or MRI) during the study.
To determine the number of patients treated with SZC who effectively need RAASi / MRA discontinuation or downtitration.
Time frame: Through study completion, an average of 1 year
Difference between mean hydration percentage with respect to baseline (OH/ECV *100) measured by multifrequency bioimpedance (BCM, Fresenius) at 90 days.
Changes in relative overhydration: (OH/ECV \*100).
Time frame: Through study completion, an average of 1 year
Proportion of patients treated with SZC presenting adverse events, in comparison to the patients non-treated with SZC, at 7, 30, 60 and 90 days
To evaluate the safety and tolerability of SZC in relation to the patients non treated with the drug.
Time frame: Through study completion, an average of 1 year
Plan to share: Undecided
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Fundación para la Investigación del Hospital Clínico de Valencia