title: Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction: Design and Rationale for Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure.
abstract: : Iron deficiency is present in ≈50% of patients with heart failure and is an independent predictor of mortality. Despite growing recognition of the functional and prognostic significance of iron deficiency, randomized multicenter trials exploring the use of oral iron supplementation in heart failure, a therapy that is inexpensive, readily available, and safe, have not been performed. Moreover, patient characteristics that influence responsiveness to oral iron in patients with heart failure have not been defined. Although results of intravenous iron repletion trials have been promising, regularly treating patients with intravenous iron products is both expensive and poses logistical challenges for outpatients. Herein, we describe the rationale for the Oral Iron Repletion effects on Oxygen Uptake in Heart Failure (IRONOUT HF) trial. This National Institute of Health-sponsored trial will investigate oral iron polysaccharide compared with matching placebo with the primary end point of change in exercise capacity as measured by peak oxygen consumption at baseline and at 16 weeks.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02188784.
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.). glewis@partners.org.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Rajeev
authors.initials: R
authors.lastname: Malhotra
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Monica R
authors.initials: MR
authors.lastname: Shah
authors.affiliation: From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L., M.J.S., R.M.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke Clinical Research Institute, Durham, NC (K.J.A., A.F.H.); Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD (M.R.S.); and Harvard Medical School, Boston, MA (E.B.).
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D058085:Iron Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects*; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D020127:Recovery of Function; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006397:Hematinics; D058085:Iron Compounds; D011134:Polysaccharides; D010100:Oxygen
keywords: clinical trial; exercise; heart failure; iron; oxygen consumption