title: Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients.
abstract: BACKGROUND
  Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration.
  
  
  METHODS
  Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin.
  
  
  RESULTS
  In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups.
  
  
  CONCLUSIONS
  FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.
authors.affiliation: Hofstra North Shore-LIJ School of Medicine, Great Neck, NY, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Fishbane
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Hôpital Charles LeMoyne, University of Sherbrooke, Québec, Canada.
authors.forename: Serge H
authors.initials: SH
authors.lastname: Cournoyer
authors.affiliation: Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AL, Canada.
authors.forename: Kailash K
authors.initials: KK
authors.lastname: Jindal
authors.affiliation: Division of Nephrology, University of Texas Health Science Center San Antonio, South Texas Veterans Health Care System, San Antonio, TX, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fanti
authors.affiliation: Rockwell Medical Inc., Wixom, MI, USA.
authors.forename: Carrie D
authors.initials: CD
authors.lastname: Guss
authors.affiliation: Rockwell Medical Inc., Wixom, MI, USA.
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Lin
authors.affiliation: Rockwell Medical Inc., Wixom, MI, USA.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Pratt
authors.affiliation: Rockwell Medical Inc., Wixom, MI, USA University of California, Irvine, Irvine, CA, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Gupta
mesh_terms: D061605:Administration, Intravenous; D018798:Anemia, Iron-Deficiency / Q000517:prevention & control*; D015314:Dialysis Solutions / Q000627:therapeutic use*; D019587:Dietary Supplements; D011756:Diphosphates / Q000627:therapeutic use*; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D015314:Dialysis Solutions; D011756:Diphosphates; D005290:Ferric Compounds; D006397:Hematinics; D006454:Hemoglobins; C025314:ferric citrate; D007501:Iron; C049051:ferric pyrophosphate
keywords: anemia; erythropoiesis-stimulating agent; ferric pyrophosphate citrate; hemodialysis; iron