A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy

David Hetzel, William Strauss, Kristine Bernard, Zhu Li, Audrone Urboniene, Lee F Allen, David Hetzel, William Strauss, Kristine Bernard, Zhu Li, Audrone Urboniene, Lee F Allen

Abstract

Iron deficiency anemia (IDA) is the most common form of anemia worldwide. Although oral iron is used as first-line treatment, many patients are unresponsive to or cannot take oral iron. This Phase III, open-label, non-inferiority study compared the efficacy and safety of ferumoxytol, a rapid, injectable intravenous (IV) iron product with low immunological reactivity and minimal detectable free iron, with IV iron sucrose in adults with IDA of any cause. Patients (N = 605) were randomized 2:1 to receive ferumoxytol (n = 406, two doses of 510 mg 5 ± 3 days apart) or iron sucrose (n = 199, five doses of 200 mg on five nonconsecutive days over 14 days) and followed for 5 weeks. Ferumoxytol demonstrated noninferiority to iron sucrose at the primary endpoint, the proportion of patients achieving a hemoglobin increase of ≥2 g dL(-1) at any time from Baseline to Week 5 (ferumoxytol, 84.0% [n = 406] vs. iron sucrose, 81.4% [n = 199]), with a noninferiority margin of 15%. Ferumoxytol was superior to iron sucrose (2.7 g dL(-1) vs. 2.4 g dL(-1) ) in the mean change in hemoglobin from Baseline to Week 5 (the alternative preplanned primary endpoint) with P = 0.0124. Transferrin saturation, quality-of-life measures, and safety outcomes were similar between the two treatment groups. Overall, ferumoxytol demonstrated comparable safety and efficacy to iron sucrose, suggesting that ferumoxytol may be a useful treatment option for patients with IDA in whom oral iron was unsatisfactory or could not be used.

Trial registration: ClinicalTrials.gov NCT01114204.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Proportion of patients with ≥2-g dL−1 increase in Hgb at any time from Baseline to Week 5 (intent-to-treat population). *Treatment difference. BL, Baseline; CI, confidence interval; Hgb, hemoglobin.
Figure 2
Figure 2
Hemoglobin values over time in patients receiving ferumoxytol or iron sucrose for up to 5 weeks (intent-to-treat population).
Figure 3
Figure 3
LS mean change in Hgb from Baseline to Week 5 (intent-to-treat population). *Treatment difference. BL, baseline; CI, confidence interval; Hgb, hemoglobin; LS, least-squares.

References

    1. World Health Organization. Worldwide Prevalence of Anaemia 1993–2005: WHO Global Database on Anaemia. Geneva: World Health Organization; 2008.
    1. Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. JAMA. 1997;277:973–976.
    1. Smith RE., Jr The clinical and economic burden of anemia. Am J Manag Care. 2010;16:S59–S66.
    1. Croker JR, Beynon G. Gastro-intestinal bleeding—A major cause of iron deficiency in the elderly. Age Ageing. 1981;10:40–43.
    1. Niv E, Elis A, Zissin R, et al. Iron deficiency anemia in patients without gastrointestinal symptoms—A prospective study. Fam Pract. 2005;22:58–61.
    1. Bermejo F, Garcia-Lopez S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol. 2009;15:4638–4643.
    1. Bayraktar UD, Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases. World J Gastroenterol. 2010;16:2720–2725.
    1. Wells CW, Lewis S, Barton JR, Corbett S. Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflamm Bowel Dis. 2006;12:123–130.
    1. World Health Organization. Iron deficiency anaemia: Assessment, prevention, and control: A guide for programme managers. Geneva, Switzerland: World Health Organization; 2001. p. 114.
    1. de Silva AD, Tsironi E, Feakins RM, Rampton DS. Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: A prospective, comparative trial. Aliment Pharmacol Ther. 2005;22:1097–1105.
    1. Provenzano R, Schiller B, Rao M, et al. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2009;4:386–393.
    1. Vifor. 2013. Venofer solution for injection or concentrate for solution for infusion: Summary of product characteristics
    1. Barton JC, Barton EH, Bertoli LF, et al. Intravenous iron dextran therapy in patients with iron deficiency and normal renal function who failed to respond to or did not tolerate oral iron supplementation. Am J Med. 2000;109:27–32.
    1. INFed®. Morristown, NY: Watson Pharma Inc; 2009. (iron dextran injection USP): US Prescribing Information.
    1. Electronic Medicines Compendium (eMC) 2014. Cosmofer. Summary of Product Characteristics. Available at: . (accessed 21 Jan )
    1. Medicines and Healthcare Products Regulatory Agency. 2013;7(1) Intravenous iron and serious hypersensitivity reactions: New strengthened recommendations to manage and minimise risk. Drug Safety Update vol, issue August : A1. Available at: . (accessed 21 Jan 2014)
    1. Auerbach M, Rodgers GM. Intravenous iron. N Engl J Med. 2007;357:93–94.
    1. Feraheme (ferumoxytol) Injection for Intravenous (IV) Use: US Prescribing Information. Lexington, MA: AMAG Pharmaceuticals Inc; 2009.
    1. Rosner MH, Auerbach M. Ferumoxytol for the treatment of iron deficiency. Expert Rev Hematol. 2011;4:399–406.
    1. Pai AB, Garba AO. Ferumoxytol: A silver lining in the treatment of anemia of chronic kidney disease or another dark cloud? J Blood Med. 2012;3:77–85.
    1. Evstatiev R, Marteau P, Iqbal T, et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology. 2011;141:846–853. e841–e842.
    1. Bisbe E, Garcia-Erce JA, Diez-Lobo AI, Munoz M. A multicentre comparative study on the efficacy of intravenous ferric carboxymaltose and iron sucrose for correcting preoperative anaemia in patients undergoing major elective surgery. Br J Anaesthesia. 2011;107:477–478.
    1. Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54:306–315.
    1. Vadhan-Raj S, Strauss W, Ford D, et al. Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron. Am J Hematol. 2014;89:7–12.
    1. Venofer (iron sucrose injection, USP) US Prescribing Information. Shirley, NY: American Regent Inc; 2011.
    1. Smith E, Lai JS, Cella D. Building a measure of fatigue: The functional assessment of chronic illness therapy fatigue scale. Pm R. 2010;2:359–363.
    1. Ware JE, Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–483.
    1. Cella D, Eton DT, Lai JS, et al. Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J Pain Symptom Manage. 2002;24:547–561.
    1. Patrick DL, Gagnon DD, Zagari MJ, et al. Assessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa. Eur J Cancer. 2003;39:335–345.
    1. Bjorner JB, Wallenstein GV, Martin MC, et al. Interpreting score differences in the SF-36 Vitality scale: Using clinical conditions and functional outcomes to define the minimally important difference. Curr Med Res Opin. 2007;23:731–739.
    1. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care. 2003;41:582–592.
    1. Singh A, Patel T, Hertel J, et al. Safety of ferumoxytol in patients with anemia and CKD. Am J Kidney Dis. 2008;52:907–915.
    1. Spinowitz BS, Kausz AT, Baptista J, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008;19:1599–1605.
    1. Schwenk MH. Ferumoxytol: A new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. Pharmacotherapy. 2010;30:70–79.
    1. McCormack PL. Ferumoxytol: In iron deficiency anaemia in adults with chronic kidney disease. Drugs. 2012;72:2013–2022.
    1. Rawal A, Katsulis P, Stutz L, et al. Presented at the National Kidney Foundation Spring Clinical Meeting. Lake Buena Vista, FL: 2013. Comparison of intravenous iron therapy for the treatment of anemia in CKD. April 2–6.
    1. Spinowitz BS, Schwenk MH, Jacobs PM, et al. The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients. Kidney Int. 2005;68:1801–1807.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren