Table 2.

Summary of patiromer clinical studies for the treatment of hyperkalemia

Study design	Patient population	Primary end point(s)	Study treatment and duration	Major findings
PEARL-HF: Phase II, prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial30	Patients with heart failure and a potassium concentration of 4.3–5.1 mEq/L (n=105) with an indication to start aldosterone-antagonist therapy	Mean change in potassium concentration from baseline to the end of the study (day 28)	Patiromer 15 g PO twice daily or placebo for 4 weeks	Baseline potassium 4.69 mEq/L; least-squares mean reduction of –0.22 mEq/L with patiromer; increase of 0.23 mEq/L with placebo (mean difference –0.45 mEq/L, P<0.001)
AMETHYST-DN: Phase II, prospective, randomized, open-label, dose-ranging clinical trial29	Outpatients with hyperkalemia (>5 mEq/L), type 2 diabetes mellitus, and CKD (eGFR 15–59 mL/min/1.73 m2) receiving an ACEi, ARB, or both (n=306)	Mean change in potassium concentration from baseline to week 4 or prior to dose titration	Patiromer 4.2 g, 8.4 g, or 12.6 g PO twice daily for 52 weeks for mild hyperkalemia (5.1–5.5 mEq/L); patiromer 8.4 g, 12.6 g, or 16.8 g PO twice daily for 52 weeks for moderate hyperkalemia (5.6–5.9 mEq/L)	Mild hyperkalemia: least-squares mean reduction of –0.35 mEq/L (95% CI –0.48 to –0.22 mEq/L) for 4.2 g group, –0.51 mEq/L (95% CI –0.64 to –0.38 mEq/L) for 8.4 g group, and –0.55 mEq/L (95% CI –0.68 to –0.42 mEq/L) for 12.6 g group (P<0.001 for each group) Moderate hyperkalemia: least-squares mean reduction of –0.87 mEq/L (95% CI –1.14 to –0.60 mEq/L) for 8.4 g group, –0.97 mEq/L (95% CI –1.23 to –0.7 mEq/L) for 12.6 g group, and –0.92 mEq/L (95% CI –1.17 to –0.67 mEq/L) for 16.8 g group (P<0.001 for each group)
OPAL-HK: Phase III prospective clinical trial with a single group, single-blind initial treatment phase and a randomized, single-blind, placebo-controlled withdrawal phase19	Initial 4-week phase: patients with stage 3 or 4 CKD (eGFR 15–59 mL/min/1.73 m2) and a potassium concentration of 5.1–6.4 mEq/L stabilized on an RAASI (n=243)	Initial phase: mean change in potassium concentration from baseline to week 4	Initial phase: patiromer 4.2 g PO for mild hyperkalemia (5.1–5.4 mEq/L) or 8.4 g PO for moderate-to-severe hyperkalemia (5.5–6.4 mEq/L) twice daily for 4 weeks	Initial phase: reduction in potassium concentration of –1.01±0.03 mEq/L (95% CI –1.07 to –0.95 mEq/L, P<0.001)
	Randomized withdrawal 8-week phase: patients with a potassium concentration of 3.8–5 mEq/L at the end of the initial phase who had potassium ≥5.5 mEq/L at baseline (n=107)	Randomized phase: between-group difference in the median change in potassium concentration over the first 4 weeks or to the earliest visit when potassium was <3.8 or ≥5.5 mEq/L	Randomized phase: continued patiromer at same dose received at week 4 or switched to placebo for 8 weeks	Randomized phase: median change in potassium concentration was an increase of 0.72 mEq/L for placebo and no change (median 0 mEq/L) for patiromer; between-group difference of –0.72 mEq/L (95% CI –0.99 to –0.46 mEq/L, P<0.001)
Phase I, prospective, open-label, single-arm clinical trial31	Patients with CKD (eGFR 15–89 mL/min/1.73 m2) and hyperkalemia (5.5–6.4 mEq/L) stabilized on an RAASI (n=25)	Change in potassium concentration from baseline over 48 hours; time of onset when mean change in potassium concentration was significant (P<0.05)	Patiromer 8.4 g PO twice daily with meals for 2 days	Baseline potassium 5.93 mEq/L; change in potassium concentration 7 hours after the first dose –0.21 mEq/L (95% CI –0.35 to –0.07 mEq/L, P=0.004); mean potassium concentration decreased to 5.41 mEq/L by 20 hours after the first dose (P<0.001)

Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; PO, per os (by mouth); RAASI, renin–angiotensin–aldosterone system inhibitor.