a prospective, randomized, open-label, cross-over study of lokelma to control interdialytic hyperkalemia

Conditions: Hyperkalemia

Summary: a prospective, randomized, multi-center, open-label, cross-over study of sodium zirconium cyclosilicate to control interdialytic hyperkalemia following augmentation of dialysate potassium: efficacy to reduce the incidence of post-dialysis atrial fibrillation and clinically significant cardiac arrhythmias - adapt trial

this is a prospective, open-labelled, randomized, 2x2 cross-over design study of 88 patients with end stage renal disease (esrd) receiving routine out-patient dialysis using a standard 2.0 potassium ion (k+)/2.5 calcium ion (ca++) dialysate bath. the overall aim of the study is to determine whether converting stable hemodialysis patients from a "standard" 2.0 k+/2.5 ca+ dialysate (without lokelma) to a 3.0 k+/2.5 ca++ meq dialysate supplemented with the orally administered potassium binder sodium zirconium cyclosilicate (lokelma) to treat interdialytic hyperkalemia will reduce the incidence and duration of post-dialysis atrial fibrillation.

Eligibility criteria:
inclusion criteria: * provision of informed consent prior to any study-specific procedures * female or male aged above 18 years * patients with esrd receiving hemodialysis three times per week for a minimum of 3 months * patients must have two (2) pre-dialysis k+ measurements between 5.1 and 6.5 meq/l by piccolo poct following the long dialytic "weekends" (i.e., on two consecutive mondays for patients on a monday-wednesday-friday dialysis schedule or on two consecutive tuesdays for patients on a tuesday-thursday-saturday dialysis schedule) during screening, before insertion of the cardiac loop recorder. * female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) they should have been stable on their chosen method of birth control for a minimum of 1 month before entering the study and willing to remain on the birth control until 4 weeks after the last dose. exclusion criteria: - exclusion criteria related to the underlying condition: * patients with a qtc(f) \> 550 msec and/or congenital long qt syndrome * patients with a haemoglobin \< 9 g/dl. * patients with any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or sponsor may pose a safety risk to a subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation. * patient receiving peritoneal or home hemodialysis * patient receiving hemodialysis via a tunneled inferior vena cava (ivc) catheter and known central stenosis of access extremity * patient receiving outpatient hemodialysis for \< 3 months * patient receiving outpatient hemodialysis for prolonged acute kidney injury (aki) and considered by the site principal investigator (pi) likely to achieve renal recovery within 6 months note: patients receiving out-patient hemodialysis for aki for longer than 6 months with no demonstrable renal clearance can be screened for study participation. * patient currently receiving a 1.0 k+, 3.0 k+ dialysate bath and unwilling to convert to a 2.0 k+/2.5 ca++ dialysate bath * subject unwilling to convert from a 2.0 k+ dialysate bath to a 3.0 k+ dialysate bath * two or more pre-dialysis k+ of \ 6.5 meq/l measured by piccolo poct after the long dialytic "weekends" during screening note: if one of the two screening pre-dialysis k+ levels is between 4.6 to 5.0 meq/l or 6.6 to 7.0 meq/l, the patient can undergo an additional whole blood piccolo poct k+ measurement. patients who fail the third whole blood piccolo poct k+ measurement will be considered ineligible for study participation. note: screen failures can be re-screened once to confirm eligibility in the study. * any documented whole blood piccolo poct k+ measurement that falls below 4.6 meq/l or exceeds 7.0 meq/l during the screening period * current use of a medication for treatment of hyperkalemia (e.g., patiromer). * note: if a medication for treatment of hyperkalemia is stopped prior to or after the consenting process, the subject will undergo a one week washout prior to the first whole blood piccolo poct k+ measurement. exclusion criteria related to other medical conditions and treatments: * anticipated life expectancy of 3 months duration * development of atrial fibrillation requiring hospitalization, medical therapy, anticoagulation, or cardioversion during study pre-screening or screening period * patient with a known placement of a dual or single chamber pacemaker * patient with an automatic implantable cardiac defibrillator (aicd) * patient with a linq implanted cardiac loop recorder with less than 6 months of battery life. * current use of amiodarone or other anti-arrhythmic therapy. note: patients on such medications must undergo a two week washout prior to the first whole blood piccolo poct k+ measurement. * known history of cardiac arrhythmias due to prolonged qt syndrome * subject unwilling to receive an implanted linq cardiac loop recorder (unless 6 months are remaining in their previously implanted device). * known active drug abuse * positive hepatitis c polymerase chain reaction (pcr) test with active viral deoxyribonucleic acid (dna) shedding or chronic active hepatitis b as evidenced by detectable surface antigen from standard of care routine dialysis labs. note: patients with negative pcr dna testing for either hepatitis b or c will be allowed to participate in the study. * known to have tested positive for human immunodeficiency virus (hiv) from standard of care routine dialysis labs. * for women only: currently pregnant (confirmed with positive pregnancy test) or breastfeeding. * patients with known and/or active severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders or diabetic gastroparesis exclusion criteria related to the investigational product (ip): * known hypersensitivity to sodium zirconium cyclosilicate (lokelmaâ). other/general exclusion criteria: * previous randomization in the present study. note: screen failures can be re-screened once to confirm eligibility in the study. * participation in another interventional (non-observational) clinical study within 4 weeks prior to enrollment in the present study