title: A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
abstract: BACKGROUND
  Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses.
  
  
  METHODS
  We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events.
  
  
  RESULTS
  Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups.
  
  
  CONCLUSIONS
  Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina; Luitpold Pharmaceuticals, Inc., Norristown, Pennsylvania; Albert Einstein College of Medicine, New York, New York; Stanford University School of Medicine, Stanford, California; Webb Writes, LLC, Durham, North Carolina; Gainesville Hematology Oncology Associates, Gainesville, Florida; Northeast OB/GYN Associates, San Antonio, Texas; Wake Gastroenterology, Wake Research Associates, Raleigh, North Carolina; Medical Oncology Care Associates, Orange, California; Grossmont Center for Clinical Research, La Mesa, California; Department of Pathology, Stanford University School of Medicine, Stanford, California.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Onken
authors.forename: David B
authors.initials: DB
authors.lastname: Bregman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: David
authors.initials: D
authors.lastname: Morris
authors.forename: Peter
authors.initials: P
authors.lastname: Acs
authors.forename: Bruce
authors.initials: B
authors.lastname: Akright
authors.forename: Charles
authors.initials: C
authors.lastname: Barish
authors.forename: Birbal S
authors.initials: BS
authors.lastname: Bhaskar
authors.forename: Gioi N
authors.initials: GN
authors.lastname: Smith-Nguyen
authors.forename: Angelia
authors.initials: A
authors.lastname: Butcher
authors.forename: Todd A
authors.initials: TA
authors.lastname: Koch
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Goodnough
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006331:Heart Diseases / Q000453:epidemiology; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D005290:Ferric Compounds; D006397:Hematinics; D006454:Hemoglobins; C522335:ferric carboxymaltose; D008320:Maltose; D007501:Iron