title: Sodium zirconium cyclosilicate in hyperkalemia.
abstract: BACKGROUND
  Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia.
  
  
  METHODS
  In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14 (maintenance phase). The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours.
  
  
  RESULTS
  At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P<0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9, serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during the maintenance phase, as compared with a level of more than 5.0 mmol per liter in the placebo group (P<0.01 for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9% and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase). Diarrhea was the most common complication in the two study groups.
  
  
  CONCLUSIONS
  Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy. (Funded by ZS Pharma; ClinicalTrials.gov number, NCT01737697.).
authors.affiliation: From the Melbourne Renal Research Group, the Department of Medicine, University of Melbourne, and the Department of Nephrology, Royal Melbourne Hospital, Melbourne, VIC (D.K.P.), and Renal Research, Gosford, NSW (S.D.R.) - both in Australia; ZS Pharma, Coppell (H.S.R., B.S.), and the University of Texas Health Science Center at San Antonio (W.Q.) and Renal Associates (P.P.), San Antonio - all in Texas; Boston Biostatistics Research Foundation, Framingham, MA (P.T.L.); Academic Medical Research Institute, Los Angeles (M.A.E.-S.), and Apex Research, Riverside (B.S.) - both in California; and Denver Nephrologists, Denver, (G.B.).
authors.forename: David K
authors.initials: DK
authors.lastname: Packham
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Rasmussen
authors.forename: Philip T
authors.initials: PT
authors.lastname: Lavin
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Shahawy
authors.forename: Simon D
authors.initials: SD
authors.lastname: Roger
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Block
authors.forename: Wajeh
authors.initials: W
authors.lastname: Qunibi
authors.forename: Pablo
authors.initials: P
authors.lastname: Pergola
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D048909:Diabetes Complications / Q000188:drug therapy; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications; D006801:Humans; D006947:Hyperkalemia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012084:Renin-Angiotensin System / Q000187:drug effects; D055502:Secondary Prevention; D017640:Silicates / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D017640:Silicates; D011188:Potassium