title: Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study.
abstract: BACKGROUND
  Unexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue.
  
  
  METHODS
  Fatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56).
  
  
  RESULTS
  The full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05-2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. 'Power of attention' improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate.
  
  
  CONCLUSIONS
  A single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency. Overall, the results support the hypothesis that iron deficiency can affect women's health, and a normal iron status should be maintained independent of hemoglobin levels.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01110356.
authors.affiliation: Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Favrat
authors.affiliation: Private Practice for Internal Medicine, Meine, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Balck
authors.affiliation: Obstetric Research & Foeto-maternal Haematology Research Group, University Hospital, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Breymann
authors.affiliation: Department of Internal Medicine, Hematology Section, Sundsvall Hospital, Sundsvall, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Hedenus
authors.affiliation: ACOMED statistic, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Keller
authors.affiliation: Vifor Pharma Ltd., Glattbrugg, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Mezzacasa
authors.affiliation: Department of Medicine 3, Medical University of Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gasche
mesh_terms: D000328:Adult; D003071:Cognition; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D004909:Erythrocyte Indices; D005221:Fatigue / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D057194:Intention to Treat Analysis; D000090463:Iron Deficiencies; D008320:Maltose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D011788:Quality of Life; D014168:Transferrin / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D006454:Hemoglobins; D010919:Placebos; D014168:Transferrin; C522335:ferric carboxymaltose; D008320:Maltose
references.citation: Am J Clin Oncol. 1982 Dec;5(6):649-55
references.pmid: 7165009
references.citation: Oncol Nurs Forum. 1998 May;25(4):677-84
references.pmid: 9599351
references.citation: BMJ. 1994 Mar 19;308(6931):763-6
references.pmid: 7908238
references.citation: Arch Intern Med. 1993 Dec 27;153(24):2759-65
references.pmid: 8257251
references.citation: Am J Clin Nutr. 2007 Mar;85(3):778-87
references.pmid: 17344500
references.citation: Expert Opin Pharmacother. 2010 Aug;11(11):1787-804
references.pmid: 20578811
references.citation: Oncology. 2011;81(1):45-9
references.pmid: 21921645
references.citation: Gut. 2012 Jun;61(6):933-52
references.pmid: 22016365
references.citation: BMJ. 2003 May 24;326(7399):1124
references.pmid: 12763985
references.citation: Clin J Am Soc Nephrol. 2006 Sep;1 Suppl 1:S4-8
references.pmid: 17699374
references.citation: Ir J Med Sci. 2002 Jan-Mar;171(1):10-2
references.pmid: 11993585
references.citation: N Engl J Med. 2009 Dec 17;361(25):2436-48
references.pmid: 19920054
references.citation: Transfusion. 2009 Dec;49(12):2719-28
references.pmid: 19682342
references.citation: CMAJ. 2012 Aug 7;184(11):1247-54
references.pmid: 22777991
references.citation: Nephrol Dial Transplant. 2011 May;26(5):1599-607
references.pmid: 20929915
references.citation: Obstet Gynecol. 2007 Aug;110(2 Pt 1):267-78
references.pmid: 17666600
references.citation: Am J Gastroenterol. 2008 May;103(5):1182-92
references.pmid: 18371137
references.citation: Ann Intern Med. 1960 Feb;52:378-94
references.pmid: 13800263
references.citation: Br J Gen Pract. 2009 Feb;59(559):e51-60
references.pmid: 19192368
references.citation: Blood. 2011 Sep 22;118(12):3191-2
references.pmid: 21940826
references.citation: Am J Clin Nutr. 2002 Apr;75(4):734-42
references.pmid: 11916761
references.citation: Int J Gynaecol Obstet. 2008 Apr;101(1):67-73
references.pmid: 18234203
references.citation: N Z Med J. 1999 May 28;112(1088):174-7
references.pmid: 10391640
references.citation: Am J Clin Nutr. 2004 Mar;79(3):437-43
references.pmid: 14985219
references.citation: Blood. 2011 Sep 22;118(12):3222-7
references.pmid: 21705493
references.citation: Methods Mol Biol. 2011;711:239-49
references.pmid: 21279605
references.citation: Eur J Clin Invest. 2002 Mar;32 Suppl 1:70-8
references.pmid: 11886435
references.citation: J Pain Symptom Manage. 2012 May;43(5):842-54
references.pmid: 22436836
references.citation: Public Health Nutr. 2001 Apr;4(2B):537-45
references.pmid: 11683548
references.citation: Eur J Clin Nutr. 1998 Jun;52(6):383-8
references.pmid: 9683388
references.citation: Am J Obstet Gynecol. 2008 Oct;199(4):435.e1-7
references.pmid: 18928998
references.citation: Gastroenterology. 2011 Sep;141(3):846-853.e1-2
references.pmid: 21699794
references.citation: Ann Oncol. 2012 Aug;23(8):1954-1962
references.pmid: 22575608
references.citation: N Engl J Med. 2013 Aug 1;369(5):448-57
references.pmid: 23902484
references.citation: Arzneimittelforschung. 2010;60(6a):399-412
references.pmid: 20648931
references.citation: Br J Haematol. 2012 Mar;156(5):588-600
references.pmid: 22512001
references.citation: Expert Opin Pharmacother. 2012 Apr;13(6):907-21
references.pmid: 22413903
references.citation: Arch Gynecol Obstet. 2010 Nov;282(5):577-80
references.pmid: 20577752
references.citation: PLoS One. 2013 Nov 18;8(11):e79576
references.pmid: 24260254