NEUTRALIZE Study: Assessing Efficacy and Safety of SZC in Hyperkalemia and Metabolic Acidosis

NKF Spring Clinical Meetings 2021

Patients with chronic kidney disease (CKD) who develop metabolic acidosis are at increased risk for cardiovascular events, mortality and progression of CKD. In previous studies, there was an association between sodium zirconium cyclosilicate (SZC), a novel potassium binder, and dose-dependent increases in serum bicarbonate.

Yasmin Brahmbhatt, MD, conducted a study to examine whether treatment with SZC can increase serum bicarbonate in a clinically meaningful way in patients with CKD-associated hyperkalemia and metabolic acidosis. The study was described during a virtual poster session at the NKF Spring Clinical Meetings 2021 in a poster titled Effect of Sodium Zirconium Cyclosilicate on Serum Potassium and Bicarbonate in Patients with Hyperkalemia and Metabolic Acidosis Associated with Chronic Kidney Disease: NEUTRALIZE Study.

NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, phase 3b study designed to assess the ability of SZC to treat hyperkalemia and increase serum bicarbonate. The mechanism behind the increase in serum bicarbonate will be examined via measurement of changes in urine ammonium. Patients will be screened using the portable blood analyzer, i-STAT, to measure potassium and bicarbonate values for eligibility.

Inclusion criteria are i-STAT results of serum potassium 5 to 5.9 mmol/L inclusive and serum bicarbonate 16 to 20 mmol/L inclusive. Eligible consenting patients will be enrolled into the open-label correction phase and will receive SZC for up to 48 hours. Follow-up will continue for 7 days following the last administration of the study medication.

The study will be conducted in the United States at nearly 35 investigative sites; approximately 400 patients will be screened and approximately 200 will be enrolled to the open-label phase in order to achieve 182 randomly assigned to study intervention.

The study has four outcomes of interest: (1) the number of patients having normal serum potassium between 3.5 and 5.0 mmol/L at the end of treatment without the need for rescue treatment for hyperkalemia; (2) the mean change in serum bicarbonate at end of treatment compared with baseline; (3) the number of patients demonstrating an increase in serum bicarbonate of ≥3 mmol/L from baseline to end of treatment without a need for rescue treatment for metabolic acidosis; and (4) safety and tolerability.

In summary, the researchers said, “NEUTRALIZE will generate evidence intended for patients and healthcare providers regarding the efficacy and safety of SZC in treating hyperkalemia and increasing serum bicarbonate.”

Source: Brahmbhatt Y, Pottorf W, Oluwatosin Y, Cooper K. Effect of sodium zirconium cyclosilicate on serum potassium and bicarbonate in patients with hyperkalemia and metabolic acidosis associated with chronic kidney disease: NEUTRALIZE study. Abstract of a poster presented at the virtual National Kidney Foundation virtual Spring Clinical Meetings 2021 (Abstract #265), April 9, 2021.