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).
Patients must present serum potassium levels of 5.5-6.5 mEq/L at patient selection visit (V0)
Patients must present serum potassium levels of 5.0-6.5 mEq/L at randomization visit (V1).
Provision of patient or legal representative informed consent prior to any study specific procedures.
Individuals receiving background standard of care for HF and treated according to locally recognized guidelines. Specific treatment should include RAASi and/or MRA treatment at first consultation and at least should have been stable for ≥ 4 weeks at maximum tolerated doses.
Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
Previous enrollment or randomization in the present study.
HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrollment.
Parallel
Sodium Zirconium Cyclosilicate
DrugThe 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.
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.
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.
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.
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.
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).
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.
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.
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).
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.
Click on the lead sponsor to view all of their trials.
