**Background:** Hyperkalemia (serum K⁺ ≥ 5.5 mEq/L) is common in hospitalized patients, occurring in up to 10% of all inpatients, and is an independent predictor of increased mortality. Risk factors include chronic kidney disease, diabetes mellitus, and use of RAAS inhibitors. For over 50 years, sodium polystyrene sulfonate (SPS, FDA-approved 1958) was the only oral potassium binder available, despite limited efficacy data in the acute setting and a black-box warning for intestinal necrosis when combined with sorbitol. Two newer agents—patiromer (FDA-approved 2015) and sodium zirconium cyclosilicate (SZC, FDA-approved 2018)—have been studied extensively for chronic hyperkalemia management but have not been compared head-to-head against each other or against SPS for acute hyperkalemia. The KBindER trial addresses this knowledge gap.
**Methods:** This is a single-center, randomized, blinded, four-arm pragmatic trial conducted at the University of California-Irvine Medical Center. Inclusion criteria: plasma K⁺ ≥ 5.5 mEq/L, age ≥ 18 years, English or Spanish speaking, able to provide written informed consent. Exclusion criteria: recent bowel surgery, ileus/bowel obstruction, potassium binder within 48 hours, hemolyzed blood specimen, severe leukocytosis (>50×10⁹/L) or thrombocytosis (>500×10⁹/L), pregnancy, active psychiatric disorder, diabetic ketoacidosis, anticipated dialysis within 4 hours, hypersensitivity to study drugs, concurrent sorbitol use. Participants are sequentially randomized to one of four groups: SPS 30 g single dose, patiromer 25.2 g single dose, SZC 15 g single dose, or polyethylene glycol 3350 17 g single dose (nonspecific laxative control). Higher doses of binders were chosen to evaluate maximum impact with one dose. Temporizing therapies (insulin/dextrose, IV fluids, albuterol, loop diuretics) are administered per treating physician discretion regardless of group assignment. Blood chemistries are drawn at 2 and 4 hours post-dose. Participants complete a Symptom Assessment form and Palatability Score at 4 hours. If 4-hour K⁺ remains ≥ 5.5 mEq/L, the primary team is notified for further management. The target enrollment is 80 patients (20 per group) to achieve 80% power to detect a 0.6 mEq/L difference in K⁺ lowering between groups (within-group SD 0.5 mEq/L, alpha 0.01). Linear mixed effects models will compare mean change in K⁺ from baseline at 2 and 4 hours and next-morning K⁺, with multivariate adjustment for kidney function, diabetes, heart failure, metabolic acidosis, RAAS inhibitor use, and concurrent temporizing agents. A Cox proportional hazards model will analyze association between binder type and length of stay. Safety and tolerability will be assessed using Kruskal-Wallis and Fisher Exact tests.
**Key Results:** The paper presents the study protocol and design; no results are reported as the trial is ongoing. The authors summarize prior evidence: SPS (30 g/day for 7 days) decreased serum K⁺ by 1.04 mEq/L vs placebo in 31 CKD outpatients (Lepage et al., P<0.001). Patiromer (single 25.2 g dose) decreased K⁺ from 6.32 to 5.91 mEq/L at 2 hours vs 6.51 mEq/L in standard of care in 30 ESRD emergency patients (Rafique et al., P<0.009). SZC (10 g dose) decreased K⁺ by 0.4 mEq/L at 2 hours in the HARMONIZE trial (Kosiborod et al., P<0.001), and in the ENERGIZE study (n=62), SZC plus insulin/glucose reduced K⁺ by −0.72±0.12 mEq/L at 2 hours vs −0.36±0.11 mEq/L with insulin/glucose alone (least squares mean difference −0.35 mmol/L; 95% CI −0.68 to −0.02).
**Clinical Implications:** The KBindER trial will provide the first direct comparative efficacy data for the three available oral potassium binders in acute hyperkalemia. Results may inform whether the higher cost of newer binders (patiromer, SZC) is justified over SPS, given SPS's association with colonic necrosis (33% mortality in 58 reported cases). The study will also assess whether potassium binders provide additional K⁺ lowering beyond standard temporizing therapies in real-world settings. If SZC demonstrates more rapid onset (1 hour vs 2–24 hours for SPS), this could influence acute management protocols. The study's pragmatic design—allowing concomitant temporizing therapies—enhances generalizability. Limitations include the single-center design, small sample size (n=80), and the study is not powered to detect superiority among binders. The findings are expected to inform decision-making guidelines for acute hyperkalemia treatment.