Clinical Efficacy, Safety, Tolerability, and Real-World Data of Patiromer for the Treatment of Hyperkalemia

Figures & data

Table 1 Summary of Patiromer Phase 1 and 2 Trials

Author (Year)	Study Design	Treatment	Number of Patients (N)	Cohort/Endpoints	Results
Pitt et al (2011)^Citation22	Randomized, double-blinded, placebo controlled	RLY5016 30 g daily and spironolactone 25 vs 50 mg daily	105	Mean change potassium from baseline, proportion of patients with hyperkalemia, proportion of patients on spironolactone 50 g daily	RLY5016 lowered potassium vs placebo, had lower hyperkalemia, and higher proportion of patients on spironolactone 50 mg. No serious AEs
Bakris et al (2015) AMETHYST-DN^Citation16	Open label, dose-ranging, randomized	Patiromer at 4.2, 8.4 g, 12.6 g, 16.8 g twice a day	306	Patients grouped as mild or moderate hyperkalemia. Mean change in serum potassium level, adverse events at 52 weeks	Patiromer lowered potassium in all groups over 52 weeks. Higher dosage reduced potassium greater. Well tolerated, highest adverse event was hypomagnesemia (7.2%)
Bushinsky et al (2015)^Citation21	Open-label, single arm	Patiromer 8.4 g twice a day	29	Mean change in potassium from baseline over 48 hrs	Patiromer had first significant lowering of potassium at 7 hours, sustained decrease over 48 hours with mean −0.75 mEq/L change
Bushinsky et al (2016)^Citation17	Double-blind, randomized, placebo-controlled, parallel group	Patiromer at 2.5, 12.6, 25.2, 50.4 g divided over 3 doses vs placebo	32	Change in urine Na, K, Mg, P, and Ca excretion	Patiromer reduced urinary Na, K, P, and Mg. Urine Ca increased but stabilized
Agarwal et al (2019)^Citation23	Double-blind, randomized, placebo-controlled,	Patiromer 8.4 g vs placebo in patients receiving spironolactone 25 mg	295	Between-group difference at 12 weeks in Spironolactone tolerance	Patiromer allowed for high proportion of patients to tolerate spironolactone (85%)

Table 2 Summary of Patiromer Phase 3 Trials

Author (Year)	Study Design	Treatment	Number of Patients (N)	Cohort/Endpoints	Results
Weir et al (2015) OPAL-HK^Citation18	Two-phase trial Part A, single-blind Part B, randomized placebo-controlled	Patiromer at 4.2 g, 8.4 g twice daily vs placebo	237	Part A, 107 patients Part B. Mean change in potassium from baseline to in Part A and Part B	Patiromer lowered potassium −1.01 mEq/L in Part A. In Part B 60% of placebo patients recurred hyperkalemia vs 15% of patiromer patients
Pergola et al (2017) TOURMALINE^Citation19	Open-label, prospective randomized	Patiromer 8.4 g/day with and without food	110	Proportion of patients with normokalemia by 3–4 weeks	Patiromer showed no clinical significance if taken with or without food. Allowed for FDA label change

Pitt B, Anker SD, Bushinsky DA, et al. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32:820–828. PMID: 21208974. doi:10.1093/eurheartj/ehq502

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Bakris GL, Pitt B, Weir MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314:151–161. PMID: 26172895. doi:10.1001/jama.2015.7446

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Bushinsky DA, Williams GH, Pitt B, et al. Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia. Kidney Int. 2015;88:1427–1433. PMID: 26376130. doi:10.1038/ki.2015.270

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Bushinsky DA, Spiegel DM, Gross C, et al. Effect of patiromer on urinary ion excretion in healthy adults. Clin J Am Soc Nephrol CJASN. 2016;11:1769–1776. PMID: 27679518. doi:10.2215/CJN.01170216

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Agarwal R, Rossignol P, Romero A, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2019;394:1540–1550. PMID: 31533906. doi:10.1016/S0140-6736(19)32135-X

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Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372:211–221. PMID: 25415805. doi:10.1056/NEJMoa1410853

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Pergola PE, Spiegel DM, Warren S, Yuan J, Weir MR. Patiromer lowers serum potassium when taken without food: comparison to dosing with food from an open-label, randomized, parallel group hyperkalemia study. Am J Nephrol. 2017;46:323–332. PMID: 29017162. doi:10.1159/000481270

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