RecruitingPhase 3NCT06578533

Keeping RAASi Treatment With Optimal Potassium Control

Phase III, Multicenter, Open-label, Randomized Clinical Trial to Evaluate Efficacy of Sodium Zirconium Cyclosilicate (Lokelma) Compared to Standard of Care to Manage Hyperkalemia in Patients With Chronic Kidney Disease (CKD)

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

Enrollment

78 participants

Start Date

Sep 30, 2022

Study Type

INTERVENTIONAL

Conditions

Chronic Kidney Diseases

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

Min Age: 18 Years

Inclusion Criteria8

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).
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 Criteria17

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.

Interventions

DRUGSodium 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.