title: 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.
abstract: OBJECTIVE
  To evaluate efficacy and safety of RLY5016 (a non-absorbed, orally administered, potassium [K+]-binding polymer) on serum K+ levels in patients with chronic heart failure (HF) receiving standard therapy and spironolactone.
  
  
  RESULTS
  One hundred and five patients with HF and a history of hyperkalaemia resulting in discontinuation of a renin-angiotensin-aldosterone system inhibitor/blocker and/or beta-adrenergic blocking agent or chronic kidney disease (CKD) with an estimated glomerular filtration rate of <60 mL/min were randomized to double-blind treatment with 30 g/day RLY5016 or placebo for 4 weeks. Spironolactone, initiated at 25 mg/day, was increased to 50 mg/day on Day 15 if K+ was ≤5.1 mEq/L. Endpoints included the change from baseline in serum K+ at the end of treatment (primary); the proportion of patients with hyperkalaemia (K+ >5.5 mEq/L); and the proportion titrated to spironolactone 50 mg/day. Safety assessments included adverse events (AEs) and clinical laboratory tests. RLY5016 (n= 55) and placebo (n= 49) patients had similar baseline characteristics. At the end of treatment, compared with placebo, RLY5016 had significantly lowered serum K+ levels with a difference between groups of -0.45 mEq/L (P < 0.001); a lower incidence of hyperkalaemia (7.3% RLY5016 vs. 24.5% placebo, P= 0.015); and a higher proportion of patients on spironolactone 50 mg/day (91% RLY5016 vs. 74% placebo, P= 0.019). In patients with CKD (n= 66), the difference in K+ between groups was -0.52 mEq/L (P= 0.031), and the incidence of hyperkalaemia was 6.7% RLY5016 vs. 38.5% placebo (P= 0.041). Adverse events were mainly gastrointestinal, and mild or moderate in severity. Adverse events resulting in study withdrawal were similar (7% RLY5016, 6% placebo). There were no drug-related serious AEs. Hypokalaemia (K+ <3.5 mEq/L) occurred in 6% of RLY5016 patients vs. 0% of placebo patients (P= 0.094).
  
  
  CONCLUSIONS
  RLY5016 prevented hyperkalaemia and was relatively well tolerated in patients with HF receiving standard therapy and spironolactone (25-50 mg/day).
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. bpitt@med.umich.edu
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: I-Zu
authors.initials: IZ
authors.lastname: Huang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006947:Hyperkalemia / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011108:Polymers / Q000009:adverse effects / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism*; D011446:Prospective Studies; D013148:Spironolactone / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D011108:Polymers; C568789:patiromer; D013148:Spironolactone; D011188:Potassium