Hyperkalemia in patients with chronic kidney disease (CKD) and heart failure history MedDRA version: 21.1 Level: LLT Classification code 10020647 Term: Hyperkalemia System Organ Class: 100000004861 MedDRA version: 23.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: LLT Classification code 10019285 Term: Heart failure, unspecified System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Lokelma
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: SODIUM ZIRCONIUM CYCLOSILICATE
Other descriptive name: SODIUM ZIRCONIUM CYCLOSILICATE
Concentration unit: g gra
Sponsors
Instituto de Investigación Sanitaria INCLIVA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must present serum potassium levels of 5.5-6.5 mEq/L at the day of inclusion. 2. Provision of patient or legal representative informed consent prior to any study specific procedures. 3. Previous history of heart failure (cardiorenal syndrome) established as a HF diagnose which has been present for at least 3 months. 4. 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. 5. Patients with CKD not on dialysis (Stages 2-5: estimated glomerular filtration rate (eGFR) between 15-60 ml/min/1,73m2 or eGFR between 60-90 ml/min/ 1.73 m2 with albuminuria/creatinuria (> 30 mg/g) in the previous three months). The estimated GFR can be reported by the laboratory or calculated by the researcher with serum creatinine, age, and sex (CKD-EPI equation). 6. At least 18 years at the time of signing ICF. 7. Negative pregnancy test (urine or serum) for female subjects of childbearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 39
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site). 2. Previous enrollment or randomization in the present study. 3. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease. 4. Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrollment. 5. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement within 12 weeks prior to enrollment or planned to undergo any of these operations after randomization). 6. Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrollment or intent to perform atrial fibrillation ablation or to implant a CRT or ICD device. 7. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization 8. Oropharingeal dysfunction that precludes normal swallow. 9. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. 10. Patients with amputated limbs or pacemaker devices will be excluded of bioimpedance analysis. 11. Participation in another clinical study with an investigational product during the last 6 months. 12. Patients with a known hypersensitivity to SZC or any of the excipients of the product. 13. Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®), within 7 days prior to the first dose of study drug. 14. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements. 15. Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc (corrected QT interval) of = 550 msec. 16. History of QT prolongation associated with other medications that required discontinuation of that medications. 17. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To analyze the proportion of patients achieving serum potassium of 20 % over the baseline at days 7, 30, 60 and 90 compared to RAASi / MRA discontinuation or downtitration. 3) To compare the 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. 4) 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). 5) To compare albuminuria changes at 90 days from baseline.;Primary end point(s): Percentage of patients achieving serum potassium < 5.5 mEq/L at three or all timepoints in both groups.;Timepoint(s) of evaluation of this end point: 7, 30, 60 or 90 days after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Percentage of patients achieving serum potassium 20% after baseline in each time point. 3) Percentage of patients achieving serum potassium below 5, 5.5, 6, 6.5 mEq/L in each time point. 4) 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. 5) 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.;Timepoint(s) of evaluation of this end point: 7, 30, 60 or 90 days after randomization | — |
Countries
Spain
Contacts
Public ContactSubdirectora Científica
Instituto de Investigación Sanitaria INCLIVA
Outcome results
None listed