Recruiting
Phase 3
Keeping RAASi Treatment With Optimal Potassium Control
Condition(s) studied
Chronic Kidney Diseases
Investigational drug(s) / intervention(s)
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.
Study summary
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).
Eligibility
Inclusion Criteria:
* 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.
* 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).
* 18 years at the time of signing ICF.
* Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
* Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of SZC. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
Exclusion Criteria:
* 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.
* 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).
* 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.
* Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization
* Oropharingeal dysfunction that precludes normal swallow.
* 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.
* Patients with amputated limbs or pacemaker devices will be excluded of bioimpedance analysis.
* Participation in another clinical study with an investigational product during the last 6 months.
* Patients with a known hypersensitivity to SZC or any of the excipients of the product.
* 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.
* 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.
* 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.
* History of QT prolongation associated with other medications that required discontinuation of that medications.
* Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
Primary outcome measure(s)
- 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. — Through study completion, an average of 1 year
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.
Trial sites (5)
| Facility | City | Region | Status |
| Hospital General Universitario Dr. Balmis |
Alicante |
Spain |
Recruiting |
| Hospital Universitario Vall d'Hebrón |
Barcelona |
Spain |
Recruiting |
| Hospital Universitario 12 de Octubre |
Madrid |
Spain |
Recruiting |
| Hospital Clínico Universitario de Valencia |
Valencia |
Spain |
Recruiting |
| Hospital Universitario Doctor Peset |
Valencia |
Spain |
Recruiting |
More Fundación para la Investigación del Hospital Clínico de Valencia trials in Spain
Other trials for the same condition