Table 3.
Summary of Trials Involving Patiromer and Sodium Zirconium Cyclosilicate (SZC)
| Trial Name | Study Design | Patient Population | Primary Aims | Study Treatment | Major Findings |
|---|---|---|---|---|---|
| PATIROMER (Veltassa) | |||||
| PEARL-HF 201185 |
Randomised, double-blind, placebo-controlled | 105 HF patients with CKD (eGFR <60 mL/min/1.73 m2) | To evaluate safety and efficacy on serum K+ levels in patients with chronic HF receiving standard therapy and spironolactone | 30 g vs placebo |
Treatment group had significantly lower serum K+ (−0.45 mEq/L; P<0.001) |
| AMETHYST-DN 201577 |
Phase 2 multicentre, open-label, dose-ranging, randomised controlled trial | 306 patients with T2DM and CKD (eGFR 15–60 mL/min/1.73 m2) on RAASi | Mean change in serum K+ from baseline to week 4 through to week 52 | Mild hyperkalemia: 8.4 g or 12.6g BD Moderate hyperkalemia: 12.6 g or 16.8 g BD |
Mean change in serum K+ at from week 4 through to week 52 (P<0.001) |
| AMBER 201986 |
Randomised, open-label, placebo-controlled | 295 patients with CKD (eGFR 25–45 mL/min/1.73m2) | Proportion of patients remaining on spironolactone | Patiromer 8.4 g vs placebo |
84% (Patiromer) vs 68% (placebo) |
| SODIUM ZIRCONIUM CYCLOSILICATE (SZC; Lokelma) | |||||
| HARMONIZE 201482 |
Phase 3, multicentre, randomised, double-blind, placebo-controlled (initial 48 h were open-label) |
258 patients with serum K+ ≥ 5.1 mEq/L | To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia. Mean serum K+ change versus placebo in each group |
10 g tds for 48 h (correction phase) Normokalaemic (3.5–5.0 mEq/L) patients randomised to 5 g, 10 g, 15 g od (maintenance phase) |
Open label (first 48 h): Serum K+ dropped from 5.6 mEq/L to 4.5 mEq/L. 84% (95% CI 79%-88% achieved normokalaemia (3.5–5.0 mEq/L). Randomised phase. Serum K+ significantly lower at each dose (P<0.001) |
| DIALIZE 201987 |
Phase 3b, multicentre, randomised, double-blind, placebo-controlled | 97 patients with ESKD and HD (x3/week), pre-dialysis serum K+ ≥ 5.4 mmol/L | Proportion of patients who maintained pre-dialysis serum K+ between 4.0–5.0 mmol/L | SZC 5 g, 10 g and 15 g vs placebo |
41.2% (treatment) vs 1.0% (placebo); P<0.001 |
| ENERGIZE 202083 |
Exploratory, Phase 2, multicentre, randomised, double-blind, placebo-controlled | 70 patients (in A&E) with serum K+ ≥ 5.8 mmol/L | Mean change in serum K+ from baseline until 4 h after initial dose. | SZC 10 g vs placebo |
Mean serum K+ change of -0.41 mmol/L (±0.11 mmol/L) |
Abbreviations: CKD, chronic kidney disease; ESKD, end-stage kidney disease; HD, hemodialysis; HF, heart failure; K+, potassium ions; RAASi, renin angiotensin aldosterone system inhibitors; SZC, sodium zirconium cyclosilicate; T2DM, type 2 diabetes mellitus.