Table 1.

Summary of the inclusion and exclusion criteria for the NEUTRALIZE study

Inclusion criteriaa	Exclusion criteriab
Age ≥18 years	Pseudohyperkalemia
Stage 3–5 CKD (eGFR ≤59 mL/min/1.73 m2) and not on dialysis	Dialysis requirement within 3 months
Two consecutive serum K+ levels (taken 1 h apart) > 5.0–≤5.9 mmol/L	History of kidney transplantation or acute/chronic worsening of kidney function (i.e., ≥30% decline in eGFR within 3 months)
Two serum HCO3– levels (taken 1 h apart) between 16 and 20 mmol/L, inclusive	Cardiac arrhythmias requiring immediate treatment; current acute decompensated HF or hospitalization for HF within 4 weeks; MI, UA, stroke, or TIA within 12 weeks; coronary revascularization within 12 weeks; or symptomatic hypotension, symptomatic or uncontrolled AF, asymptomatic VT, or QT prolongation
Able to undergo repeated blood draws or effective venous catheterization	Low HCO3– requiring emergency intervention or treatment
Informed consent	Active or suspected diabetic ketoacidosis; history of diabetic gastroparesis; bariatric surgery; bowel obstruction; or swallowing disorders
	Current exacerbation of COPD/asthma or hospitalization for COPD/asthma within 4 weeks
	Active malignancy requiring treatment
	Life expectancy of <3 months
	Active treatment (within 7 days prior to screening) with a K+ binder (i.e., SZC, SPS, or patiromer), sodium bicarbonate, or lactulose
	Prior or concurrent participation in another clinical study with the administration of study drug within 1 month
	Known hypersensitivity to SZC
	Current pregnancy
	Evidence of COVID-19 within 2 weeks prior to screening

AF, atrial fibrillation; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; HCO₃^–, bicarbonate; HF, heart failure; K⁺, potassium; MI, myocardial infarction; SPS, sodium polystyrene sulfonate; SZC, sodium zirconium cyclosilicate; TIA, transient ischemic attack; UA, unstable angina; VT, ventricular tachycardia.

^aEligible participants must meet all of the inclusion criteria.

^bParticipants are excluded if any of the exclusion criteria are met.