PMID- 21208974 OWN - NLM STAT- MEDLINE DCOM- 20111227 LR - 20220331 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 32 IP - 7 DP - 2011 Apr TI - 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. PG - 820-8 LID - 10.1093/eurheartj/ehq502 [doi] AB - AIMS: 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. METHODS AND 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 5.5 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). CONCLUSION: RLY5016 prevented hyperkalaemia and was relatively well tolerated in patients with HF receiving standard therapy and spironolactone (25-50 mg/day). FAU - Pitt, Bertram AU - Pitt B AD - University of Michigan, Ann Arbor, MI, USA. bpitt@med.umich.edu FAU - Anker, Stefan D AU - Anker SD FAU - Bushinsky, David A AU - Bushinsky DA FAU - Kitzman, Dalane W AU - Kitzman DW FAU - Zannad, Faiez AU - Zannad F FAU - Huang, I-Zu AU - Huang IZ CN - PEARL-HF Investigators LA - eng SI - ClinicalTrials.gov/NCT00868439 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20110105 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Polymers) RN - 1FQ2RY5YHH (patiromer) RN - 27O7W4T232 (Spironolactone) RN - RWP5GA015D (Potassium) SB - IM CIN - Eur Heart J. 2011 Apr;32(7):791-2. PMID: 21383002 MH - Adrenergic beta-Antagonists/therapeutic use MH - Aged MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use MH - Chronic Disease MH - Double-Blind Method MH - Female MH - Heart Failure/blood/complications/*drug therapy MH - Humans MH - Hyperkalemia/*prevention & control MH - Kidney Failure, Chronic/complications MH - Male MH - Middle Aged MH - Mineralocorticoid Receptor Antagonists/*therapeutic use MH - Polymers/adverse effects/*therapeutic use MH - Potassium/*metabolism MH - Prospective Studies MH - Spironolactone/therapeutic use MH - Treatment Outcome MH - Young Adult PMC - PMC3069389 FIR - Adler, Alexander IR - Adler A FIR - Akatova, Evgenia IR - Akatova E FIR - Anand, Inder IR - Anand I FIR - Baliga, Ragavendra IR - Baliga R FIR - Banerjee, Subhash IR - Banerjee S FIR - Barbarash, Olga IR - Barbarash O FIR - Chumburidze, Vakhtang IR - Chumburidze V FIR - Goloshchekin, Boris M IR - Goloshchekin BM FIR - Gordeev, Ivan IR - Gordeev I FIR - Holland, Joanne IR - Holland J FIR - Hotchkiss, David IR - Hotchkiss D FIR - Iacona, Marie IR - Iacona M FIR - Khintibidze, Irakli IR - Khintibidze I FIR - Malek, Ivan IR - Malek I FIR - Natour, Mohammed IR - Natour M FIR - Paposhvili, Kakhi IR - Paposhvili K FIR - Parkhomenko, Alexander IR - Parkhomenko A FIR - Roberts, Jonathan IR - Roberts J FIR - Shaburishvili, Tamaz IR - Shaburishvili T FIR - Spinar, Jindrich IR - Spinar J FIR - Svyshchenko, Yevgenia IR - Svyshchenko Y FIR - Szwed, Hanna IR - Szwed H FIR - Vishnevsky, Alexander IR - Vishnevsky A FIR - Wachter, Rolf IR - Wachter R FIR - Zebrack, James IR - Zebrack J FIR - Albrecht, Detlef IR - Albrecht D FIR - Burdick, Mike IR - Burdick M FIR - Buysse, Jerry IR - Buysse J FIR - Cope, Michael Jamie IR - Cope MJ FIR - Halfon, Sherin IR - Halfon S FIR - Jone, Ming IR - Jone M FIR - Stasiv, Yuri IR - Stasiv Y FIR - Warren, Suzette IR - Warren S EDAT- 2011/01/07 06:00 MHDA- 2011/12/28 06:00 PMCR- 2011/01/05 CRDT- 2011/01/07 06:00 PHST- 2011/01/07 06:00 [entrez] PHST- 2011/01/07 06:00 [pubmed] PHST- 2011/12/28 06:00 [medline] PHST- 2011/01/05 00:00 [pmc-release] AID - ehq502 [pii] AID - 10.1093/eurheartj/ehq502 [doi] PST - ppublish SO - Eur Heart J. 2011 Apr;32(7):820-8. doi: 10.1093/eurheartj/ehq502. Epub 2011 Jan 5.