title: The Ferumoxytol for Anemia of CKD Trial (FACT)-a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale.
abstract: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis.
  
  
  
  The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An "oxidative stress" substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months.
  
  
  
  FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon.
  
  
  
  ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28.
authors.affiliation: Department of Renal Medicine, King's College Hospital, Denmark Hill, London, UK.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.affiliation: AMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Naomi V
authors.initials: NV
authors.lastname: Dahl
authors.affiliation: AMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Bernard
authors.affiliation: AMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: AMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Alka
authors.initials: A
authors.lastname: Batycky
authors.affiliation: AMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA, 02451, USA. wstrauss@amagpharma.com.
authors.forename: William E
authors.initials: WE
authors.lastname: Strauss
mesh_terms: D061605:Administration, Intravenous; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000209:etiology; D005290:Ferric Compounds / Q000627:therapeutic use*; D000077605:Ferric Oxide, Saccharated; D052203:Ferrosoferric Oxide / Q000627:therapeutic use*; D005937:Glucaric Acid / Q000627:therapeutic use*; D006321:Heart / Q000000981:diagnostic imaging; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008099:Liver / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D010179:Pancreas / Q000000981:diagnostic imaging; D006435:Renal Dialysis
chemical_list: D005290:Ferric Compounds; D006397:Hematinics; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D052203:Ferrosoferric Oxide
keywords: Chronic kidney disease; Ferumoxytol; Hemodialysis; Iron overload; Iron sucrose; Oxidative stress