Abstract
Background and Aims
Patients with end-stage renal disease (ESRD) on chronic haemodialysis are at an elevated risk of arrhythmias that can increase the risk of sudden cardiac death (SCD) and stroke, along with the need for hospitalisation and interventions. These arrhythmias may be exacerbated by pre-dialysis hyperkalaemia and rapid serum potassium (sK+) shifts that occur during and after haemodialysis sessions. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an effective and well-tolerated treatment for pre-dialysis hyperkalaemia, when administered once-daily on non-dialysis days for 8 weeks in patients with ESRD undergoing chronic haemodialysis. The DIALIZE-Outcomes study (EudraCT 2020-005561-14) will evaluate the effect of SZC treatment on arrhythmia-related cardiovascular (CV) outcomes in patients with ESRD on chronic haemodialysis with recurrent hyperkalaemia.
Method
The DIALIZE-Outcomes study is an international, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, to be conducted at ∼300 study sites across ∼20 countries. Adults (≥18 years of age) with ESRD on haemodialysis three times weekly and with recurrent pre-dialysis sK+ ≥5.5 mmol/L after the long interdialytic interval (LIDI) will be eligible for enrolment. Approximately 2300 patients will be randomised 1:1 to SZC or placebo (Figure), starting at 5 g orally once daily on non-dialysis days (4 days/week) and uptitrated weekly in 5 g increments (maximum 15 g) to achieve pre-dialysis sK+ 4.0–5.0 mmol/L after the LIDI. Dose adjustments after the uptitration phase will be guided by sK+ monitoring, as per clinical practice. The primary objective is to evaluate the efficacy of SZC versus placebo in reducing the incidence of the primary composite endpoint of time to first occurrence of SCD, stroke or hospitalisation/intervention/emergency department visit due to arrhythmias (atrial fibrillation, bradycardia, asystole, ventricular tachyarrhythmia). Secondary endpoints include the efficacy of SZC versus placebo in maintaining normokalaemia (sK+ 4.0–5.5 mmol/L after the LIDI) and preventing severe hyperkalaemia (sK+ ≥6.5 mmol/L after the LIDI) at 1 year (assessed through measurement of sK+ at the 12-month study visit), and time to occurrence of CV outcomes. Safety and tolerability of SZC versus placebo will also be evaluated. The study is event-driven, with patients remaining on study treatment until a pre-specified number of primary endpoint events (770) has occurred. The anticipated average treatment period is ∼25 months.
Conclusion
The DIALIZE-Outcomes study is the first evaluation of a K+ binder in improving CV outcomes in patients with ESRD on chronic haemodialysis and with recurrent hyperkalaemia. The study findings will provide valuable information that may help to further our understanding of the relationship between hyperkalaemia and CV morbidity and mortality in patients on chronic haemodialysis, and to optimise treatment regimens in this high CV and SCD risk population.
MO214EVALUATION OF THE EFFECT OF A POTASSIUM BINDER ON ARRHYTHMIA-RELATED CARDIOVASCULAR OUTCOMES IN PATIENTS ON CHRONIC HAEMODIALYSIS WITH RECURRENT HYPERKALAEMIA: DESIGN AND RATIONALE FOR THE SODIUM ZIRCONIUM CYCLOSILICATE DIALIZE-OUTCOMES STUDY
