Efficacy and Safety of Sodium Zirconium Cyclosilicate in the Management of Hyperkalemia in Patients with Heart Failure with Reduced and Mildly Reduced Ejection Fraction and Chronic Kidney Disease Treated with Spironolactone: rational for and design of the REGISTA-K trial.

Background: To evaluate whether sodium zirconium cyclosilicate (SZC) enables the uptitration of spironolactone without increasing the risk of hyper- and hypokalemia in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) and moderate/severe chronic kidney disease (CKD) who developed hyperkalemia during treatment with suboptimal spironolactone dose.

Methods: The REGISTA-K is a randomized, double-blind, placebo-controlled, multicenter trial that examined the efficacy and safety of SZC in uptitrating spironolactone without the occurrence of hyperkalemia or hypokalemia. A total of 266 patients with HFrEF and HFmrEF and hyperkalemia will be randomized in a 1:1 ratio to receive either SZC or placebo after treating hyperkalemia with SZC at 25 sites in Japan. The study enrolls patients with left ventricular EF <50%, moderate/severe CKD (estimated glomerular filtration rate 15-45 mL/min/1.73 m), serum potassium level >5.0 mEq/L, and undergoing 12.5-37.5 mg spironolactone treatment. The primary endpoint is successful administration of 50 mg/day spironolactone at 16 weeks follow-up without the need for rescue therapy for either hypokalemia or hyperkalemia.

Conclusions: REGISTA-K will evaluate the efficacy and safety of SZC as adjunctive therapy in uptitrating spironolactone in patients with HFrEF and HFmrEF with moderate to severe renal dysfunction and hyperkalemia.