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Meta-Analysis
. 2014 Dec 31;2014(12):CD010640.
doi: 10.1002/14651858.CD010640.pub2.

Iron therapy in anaemic adults without chronic kidney disease

Kurinchi Selvan Gurusamy  1 , Myura Nagendran, Jack F Broadhurst, Stefan D Anker, Toby Richards
Affiliations
Meta-Analysis

Iron therapy in anaemic adults without chronic kidney disease

Kurinchi Selvan Gurusamy et al. Cochrane Database Syst Rev. .

Abstract

Background: Anaemia affects about a quarter of the world's population. An estimated 50% of anaemic people have anaemia due to iron deficiency.

Objectives: To assess the safety and efficacy of iron therapies for the treatment of adults with anaemia who are not pregnant or lactating and do not have chronic kidney disease.

Search methods: We ran the search on 11 July 2013. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE (Ovid SP), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus (EBSCO Host), the Institute for Scientific Information Web of Science (ISI WOS) Scientific Citation Index (SCI)-EXPANDED (1970) and Conference Proceedings Citation Index (CPCI)-Science (1990) and Clinicaltrials.gov; we also screened reference lists. An updated search was run on 24 November 2014 but the results have not yet been incorporated into the review.

Selection criteria: Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full-text articles for selected references.

Data collection and analysis: Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes and the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes. We performed meta-analysis when possible, when I(2) was less than or equal to 80% using a fixed-effect or random-effects model, using Review Manager software. The range of point estimates for individual studies is presented when I(2) > 80%.

Main results: We included in this systematic review 4745 participants who were randomly assigned in 21 trials. Trials were conducted in a wide variety of clinical settings. Most trials included participants with mild to moderate anaemia and excluded participants who were allergic to iron therapy. All trials were at high risk of bias for one or more domains. We compared both oral iron and parenteral iron versus inactive controls and compared different iron preparations.The comparison between oral iron and inactive control revealed no evidence of clinical benefit in terms of mortality (RR 1.05, 95% CI 0.68 to 1.61; four studies, N = 659; very low-quality evidence). The point estimate of the mean difference in haemoglobin levels in individual studies ranged from 0.3 to 3.1 g/dL higher in the oral iron group than in the inactive control group. The proportion of participants who required blood transfusion was lower with oral iron than with inactive control (RR 0.74, 95% CI 0.55 to 0.99; three studies, N = 546; very low-quality evidence). Evidence was inadequate for determination of the effect of parenteral iron on mortality versus oral iron (RR 1.49, 95% CI 0.56 to 3.94; 10 studies, N = 2141; very low-quality evidence) or inactive control (RR 1.04, 95% CI 0.63 to 1.69; six studies, N = 1009; very low-quality evidence). Haemoglobin levels were higher with parenteral iron than with oral iron (MD -0.50 g/dL, 95% CI -0.73 to -0.27; six studies, N = 769; very low-quality evidence). The point estimate of the mean difference in haemoglobin levels in individual studies ranged between 0.3 and 3.0 g/dL higher in the parenteral iron group than in the inactive control group. Differences in the proportion of participants requiring blood transfusion between parenteral iron and oral iron groups (RR 0.61, 95% CI 0.24 to 1.58; two studies, N = 371; very low-quality evidence) or between parenteral iron groups and inactive controls (RR 0.84, 95% CI 0.66 to 1.06; eight studies, N = 1315; very low-quality evidence) were imprecise. Average blood volume transfused was less in the parenteral iron group than in the oral iron group (MD -0.54 units, 95% CI -0.96 to -0.12; very low-quality evidence) based on one study involving 44 people. Differences between therapies in quality of life or in the proportion of participants with serious adverse events were imprecise (very low-quality evidence). No trials reported severe allergic reactions due to parenteral iron, suggesting that these are rare. Adverse effects related to oral iron treatment included nausea, diarrhoea and constipation; most were mild.Comparisons of one iron preparation over another for mortality, haemoglobin or serious adverse events were imprecise. No information was available on quality of life. Thus, little evidence was found to support the use of one preparation or regimen over another.Subgroup analyses did not reveal consistent results; therefore we were unable to determine whether iron is useful in specific clinical situations, or whether iron therapy might be useful for people who are receiving erythropoietin.

Authors' conclusions: • Very low-quality evidence suggests that oral iron might decrease the proportion of people who require blood transfusion, and no evidence indicates that it decreases mortality. Oral iron might be useful in adults who can tolerate the adverse events, which are usually mild.• Very low-quality evidence suggests that intravenous iron results in a modest increase in haemoglobin levels compared with oral iron or inactive control without clinical benefit.• No evidence can be found to show any advantage of one iron preparation or regimen over another.• Additional randomised controlled trials with low risk of bias and powered to measure clinically useful outcomes such as mortality, quality of life and blood transfusion requirements are needed.

PubMed Disclaimer

Conflict of interest statement

KSG: none known.

MN: none known.

JFB: none known.

SDA: (in part through employer) has received grants and fees for lectures, consultancy and/or board membership from Abbott Vascular, Amgen, Bayer, BG Medicine, Bioventrix, Brahms, Cardiomems, Novartis, BG Medicine, Impulse Dynamics, Medical Sensible, Pluristem, Psioxus, Relypsa, Servier and/or Vifor.

TR: UCL received an educational grant from Vifor Pharma in 2009. This funded a research fellow who undertook an audit of anaemia in surgical patients. These data have been presented at national and international meetings. TR is currently Chief Investigator for an NIHR HTA trial that is being conducted to assess the role of Intravenous iron in the treatment of individuals with anaemia before major surgery (PREVENTT). No funding was provided for this Cochrane review, and no input was received from anyone other than study authors. TR received travel funds from the BBTS, NATA, Pharmocosmos, Vifor Pharma and other industry.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Twenty‐one studies are included in this review.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 2 Proportion requiring blood transfusion.
1.3
1.3. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 3 Length of hospital stay.
1.4
1.4. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 4 Haemoglobin.
1.5
1.5. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 5 Quality of life.
1.6
1.6. Analysis
Comparison 1 Oral iron vs inactive control, Outcome 6 Serious adverse events.
2.1
2.1. Analysis
Comparison 2 Parenteral iron vs inactive control, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Parenteral iron vs inactive control, Outcome 2 Proportion requiring blood transfusion.
2.3
2.3. Analysis
Comparison 2 Parenteral iron vs inactive control, Outcome 3 Haemoglobin.
2.4
2.4. Analysis
Comparison 2 Parenteral iron vs inactive control, Outcome 4 Quality of life.
2.5
2.5. Analysis
Comparison 2 Parenteral iron vs inactive control, Outcome 5 Serious adverse events.
3.1
3.1. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 1 Mortality.
3.2
3.2. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 2 Proportion requiring blood transfusion.
3.3
3.3. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 3 Mean blood transfused.
3.4
3.4. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 4 Haemoglobin.
3.5
3.5. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 5 Quality of life.
3.6
3.6. Analysis
Comparison 3 Parenteral iron vs oral iron, Outcome 6 Serious adverse events.
4.1
4.1. Analysis
Comparison 4 Iron: different preparations, Outcome 1 Mortality.
4.2
4.2. Analysis
Comparison 4 Iron: different preparations, Outcome 2 Haemoglobin.
4.3
4.3. Analysis
Comparison 4 Iron: different preparations, Outcome 3 Serious adverse events.
5.1
5.1. Analysis
Comparison 5 Subgroup analysis, Outcome 1 Mortality (parenteral iron vs inactive control stratified by clinical setting).
5.2
5.2. Analysis
Comparison 5 Subgroup analysis, Outcome 2 Mortality (parenteral iron vs inactive control stratified by erythropoietin use).
5.3
5.3. Analysis
Comparison 5 Subgroup analysis, Outcome 3 Mortality (parenteral iron vs oral iron stratified by clinical setting).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010640

References

References to studies included in this review

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Evstatiev 2011 {published data only}
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Hedenus 2007 {published data only}
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Hetzel 2012 {published data only}
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Karkouti 2006 {published data only}
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References to studies excluded from this review

Anker 2006 {published data only}
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    1. Gasche C, Dejaco C, Waldhor T, Reinisch W, Tillinger W, Vogelsang H, et al. [Double‐blind, placebo‐controlled study of erythropoietin and iron saccharate in the treatment of anaemia in Crohn's disease]. Zeitschrift fur Gastroenterologie 1995;33(5):320.
Gedik 1995 {published data only}
    1. Gedik Y, Erduran E, Mocan H, Aynaci FM, Okten A. The efficacy of ferrous sulfate and ferric polymaltose in therapy of iron deficiency anemia. Annals of Medical Sciences 1995;4(2):143‐4.
Grote 2009 {published data only}
    1. Grote L, Leissner L, Hedner J, Ulfberg J. A randomized, double‐blind, placebo controlled, multi‐center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Movement Disorders 2009;24(10):1445‐52. - PubMed
Harris 2009 {published data only}
    1. Harris S, Tepper D, Ip R. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency‐ferric‐HF: a randomized, controlled, observer‐blinded trial. Congestive Heart Failure 2009;15(4):208. - PubMed
Hussain 2013 {published data only}
    1. Hussain I, Bhoyroo J, Butcher A, Koch TA, He A, Bregman DB. Direct comparison of the safety and efficacy of ferric carboxymaltose versus iron dextran in patients with iron deficiency anemia. Anemia 2013;2013:169107. - PMC - PubMed
Kaltwasser 1987 {published data only}
    1. Kaltwasser JP, Ockelmann R, Schalk KP. Oral iron therapy: preparations with rapid or delayed iron liberation?. Medizinische Klinik 1987;82(21):730‐5. - PubMed
Kaltwasser 1989 {published data only}
    1. Kaltwasser JP, Schwarz‐Van d SW. Oral iron treatment: bioavailability and therapeutic efficacy of ferrous iron as effervescent tablets in posthaemorrhagic iron‐deficiency anaemia. Deutsche Medizinische Wochenschrift 1989;114(31‐32):1188‐95. - PubMed
Kulnigg 2009 {published data only}
    1. Kulnigg S, Teischinger L, Dejaco C, Waldhor T, Gasche C. Rapid recurrence of IBD‐associated anemia and iron deficiency after intravenous iron sucrose and erythropoietin treatment. American Journal of Gastroenterology 2009;104(6):1460‐7. - PubMed
Kulnigg‐Dabsch 2012 {published data only}
    1. Kulnigg‐Dabsch S, Evstatiev R, Dejaco C, Gasche C. Effect of iron therapy on platelet counts in patients with inflammatory bowel disease‐associated anemia. PLoS ONE 2012;7(4):e34520. - PMC - PubMed
Lewinski 1973 {published data only}
    1. Lewinski U, Lijn E, Djaldetti M. [Intravenous iron‐dextran versus peroral iron and blood transfusion for anemia]. Harefuah 1973;85(4):167‐9. - PubMed
Liguori 1993 {published data only}
    1. Liguori L. Iron protein succinylate in the treatment of iron deficiency: controlled, double‐blind, multicenter clinical trial on over 1,000 patients. International journal of Clinical Pharmacology, Therapy, and Toxicology 1993;31(3):103‐23. - PubMed
Lipsic 2010 {published data only}
    1. Lipsic E, Meer P. Erythropoietin, iron, or both in heart failure: FAIR‐HF in perspective. European Journal of Heart Failure 2010;12(2):104‐5. - PubMed
Littlewood 2012 {published data only}
    1. Littlewood TJ. Intravenous or oral iron?. American Journal of Hematology 2012;87(2):134‐5. - PubMed
Liu 2004 {published data only}
    1. Liu TC, Lin SF, Chang CS, Yang WC, Chen TP. Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. International Journal of Hematology 2004;80(5):416‐20. - PubMed
Mundy 2005 {published data only}
    1. Mundy GM, Birtwistle SJ, Power RA. The effect of iron supplementation on the level of haemoglobin after lower limb arthroplasty. The Journal of Bone and Joint Surgery. British Volume 2005;87(2):213‐7. - PubMed
Munoz 2011 {published data only}
    1. Munoz M, Naveira E, Seara J, Cordero J, Marcos F, Bisbe E. Postoperative intravenous iron after lower limb arthroplasty: a comparative study of different doses on transfusion requirements. European Journal of Anaesthesiology 2011;28:90.
Munoz 2011a {published data only}
    1. Munoz M, Naveira E, Seara J, Cordero J, Martos F. Postoperative iron after lower limb arthroplasty: a comparative study of the effects of 300 vs. 600 mg IV iron administration on transfusion requirements. Transfusion Alternatives in Transfusion Medicine 2011;12(1):34‐5.
Munoz 2012 {published data only}
    1. Munoz M, Naveira E, Seara J, Cordero J. Effects of postoperative intravenous iron on transfusion requirements after lower limb arthroplasty. British Journal of Anaesthesia 2012;108(3):532‐4. - PubMed
Murgel 1969 {published data only}
    1. Murgel GA. Therapy of hypochromic anemia using ferrous sulfate (comparative study of reinforced sustained‐release pills and conventional pills). Revista Brasileira de Medicina 1969;26(6):375‐9. - PubMed
Najean 1995 {published data only}
    1. Najean Y, Acuto G, Scotti A. Multicentre double‐blind clinical trial of iron protein succinylate in comparison with iron sulfate in the treatment of iron deficiency anaemia. Clinical Drug Investigation 1995;10(4):198‐207.
Onken 2013 {published data only}
    1. Bregman DB, Morris D, Koch TA, He A, Goodnough LT. Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. American Journal of Hematology 2013;88(2):97‐101. - PubMed
    1. Onken JE, Bregman DB, Harrington RA, Morris D, Acs P, Akright B, 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 2013; Vol. Epub ahead of print. - PubMed
Ravanbod 2013 {published data only}
    1. Ravanbod M, Asadipooya K, Kalantarhormozi M, Nabipour I, Omrani GR. Treatment of iron‐deficiency anemia in patients with subclinical hypothyroidism. American Journal of Medicine 2013;126(5):420‐4. - PubMed
Raya 2010 {published data only}
    1. Raya J, Garrido P, Pecos P, Martinez R, Nassar I, Llana R, et al. Analysis of two different schemes of iron treatment to improve postoperative anemia in cardiac surgery: a randomized double‐disguised, triple‐blind study. Haematologica 2010;95(Suppl 2):706.
Rondinelli 2013 {published data only}
    1. Rondinelli MB, Inghilleri G, Pavesi M, Bartolomei A, Pagnotta R, Terlizzi F, et al. Efficacy of ferrous bisglycinate for the management of patient undergoing pre‐operative blood donation or with pre‐operative anaemia in orthopedic surgery: a prospective study. Transfusion Medicine 2013;23(s1):36.
Schatz 2013 {published data only}
    1. Schatz U, Arneth B, Siegert G, Siegels D, Fischer S, Julius U, et al. Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations. Atherosclerosis Supplements 2013;14(1):115‐22. - PubMed
Serrano‐Trenas 2011 {published data only}
    1. Serrano‐Trenas JA, Ugalde PF, Cabello LM, Chofles LC, Lazaro PS, Benitez PC. Role of perioperative intravenous iron therapy in elderly hip fracture patients: a single‐center randomized controlled trial. Transfusion 2011;51(1):97‐104. - PubMed
Singh 2007 {published data only}
    1. Singh A, Hertel J, Bernardo M, Baptista J, Kausz A, Brenner L, et al. A double‐blind, placebo‐controlled, randomized phase III study of the safety of ferumoxytol as a new intravenous iron replacement therapy. American Journal of Kidney Diseases 2007;49(4):A32.
Strauss 2013 {published data only}
    1. Strauss W, Bernard K, Li Z, Allen L. Safety and efficacy of ferumoxytol vs. iron sucrose in the treatment of iron deficiency anemia (IDA) in patients with normal and abnormal renal function. Nephrology Dialysis Transplantation 2013;28(Suppl 1):i9.
Wang 2003 {published data only}
    1. Wang L, Li G, Liao C, Wang F. The effects of oral vs venous iron supplement in treatment of iron deficiency of maintained patients with anemia [Abstract No. PUB324]. Journal of the American Society of Nephrology 2003;14(Suppl S):842a.
Weatherall 2004 {published data only}
    1. Weatherall M, Maling TJ. Oral iron therapy for anaemia after orthopaedic surgery: randomized clinical trial. ANZ Journal of Surgery 2004;74(12):1049‐51. - PubMed
Zauber 1992 {published data only}
    1. Zauber NP, Zauber AG, Gordon FJ, Tillis AC, Leeds HC, Berman E, et al. Iron supplementation after femoral head replacement for patients with normal iron stores. JAMA 1992;267(4):525‐7. - PubMed

References to studies awaiting assessment

Adsul 2005 {published data only}
    1. Adsul BB, Desai A, Gawde A, Baliga V. Comparative assessment of the bioavailability, efficacy and safety of a modified‐release (MR) carbonyl iron tablet and oral conventional iron preparation in adult Indian patients with nutritional iron deficiency anaemia. Journal of the Indian Medical Association 2005;103(6):338‐42. - PubMed
Anthony 2011 {published data only}
    1. Anthony LB, Gabrail NY, Ghazal H, Woytowitz DV, Flam MS, Drelichman A, et al. IV iron sucrose for cancer and/or chemotherapy‐induced anemia in patients treated with erythropoiesis stimulating agents. Community Oncology 2011;8(6):270‐8.
    1. Bellet RE, Ghazal H, Flam M, Drelichman A, Gabrail N, Woytowitz D, et al. A phase III randomized controlled study comparing iron sucrose intravenously (IV) to no iron treatment of anemia in cancer patients undergoing chemotherapy and erythropoietin stimulating agent (ESA) therapy [Abstract No. 9109]. Journal of Clinical Oncology 2007;25(18S Part I):519.
Auerbach 2004 {published data only}
    1. Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy‐related anemia: a multicenter, open‐label, randomized trial. Journal of Clinical Oncology 2004;22(7):1301‐7. - PubMed
    1. Auerbach M, Barker L, Bahrain H, Trout R, McIlwain M, Ballard H. Intravenous iron (IV Fe) optimizes the response to erythropoietin (EPO) in patients with anemia of cancer and cancer chemotherapy: results of a multicenter, open‐label, randomized trial. Blood 2001;98(11):799A. - PubMed
    1. Ballard H, Rana J, Ackerman A, Merino R, Rosenoff S, Kastritsis C, et al. Total dose infusion (TDI) of iron dextran (ID) optimizes erythropoietin (EPO) responsiveness in the anemia of cancer (CA) [abstract]. Proceedings of the American Society of Clinical Oncology 1999;18:581a.
Bisbe 2012 {published data only}
    1. Bisbe E. Intravenous iron to treat post‐operative anaemia. Transfusion Medicine 2013;23(s1):13‐4.
    1. Bisbe E. Intravenous iron to treat postoperative anaemia. Vox Sanguinis 2013;105(Suppl 1):50.
    1. Bisbe E, Molto L, Arroyo R, Santiveri X, Munoz M. The efficacy of intravenous iron for treating postoperative anemia and hastening functional recovery in patients undergoing total knee arthroplasty: preliminary results from a randomized controlled trial. Transfusion Alternatives in Transfusion Medicine 2012;12(2):29‐30.
Chen 2002 {published data only}
    1. Chen BB, Lin GW, Wu W, Chen Y, Wang JE, Wang YL. Comparitive study on three iron preparations for treatment of iron deficiency anemia: a randomized‐controlled trial. Shanghai Medical Journal 2002;25(3):154‐7.
Devasthali 1991 {published data only}
    1. Devasthali SD, Gordeuk VR, Brittenham GM, Bravo JR, Hughes MA, Keating LJ. Bioavailability of carbonyl iron: a randomized, double‐blind study. European Journal of Haematology 1991;46(5):272‐8. - PubMed
Erichsen 2005 {published data only}
    1. Erichsen K, Ulvik RJ, Grimstad T, Berstad A, Berge RK, Hausken T. Effects of ferrous sulphate and non‐ionic iron‐polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 2005;22(9):831‐8. - PubMed
    1. Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, et al. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scandinavian Journal of Gastroenterology 2005;40(9):1058‐65. - PubMed
Ferrari 2012 {published data only}
    1. Ferrari P, Nicolini A, Manca ML, Rossi G, Anselmi L, Conte M, et al. Treatment of mild non‐chemotherapy‐induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate. Biomedicine and Pharmacotherapy 2012; Vol. Epub ahead of print. - PubMed
Giordano 2011 {published data only}
    1. Giordano G, Mondello P, Tambaro R, Maria M, D'Amico F, Sticca G, et al. Intravenous iron support vs oral liposomal iron support in patients with refractory anemia treated with Epo alpha. Monocentric prospective study. Leukemia Research 2011;35:S137.
Gordeuk 1987 {published data only}
    1. Gordeuk VR, Brittenham GM, Hughes M, Keating LJ, Opplt JJ. High‐dose carbonyl iron for iron deficiency anemia: a randomized double‐blind trial. The American Journal of Clinical Nutrition 1987;46(6):1029‐34. - PubMed
Henry 2007 {published data only}
    1. Henry DH, Dahl NV. Does quality of life improvement precede anemia correction in patients with chemotherapy‐induced anemia treated with intravenous iron? [abstract]. Journal of Clinical Oncology 2007;25(18S Part I):513.
    1. Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR. Intravenous ferric gluconate (FG) for increasing response to epoetin (EPO) in patients with anemia of cancer chemotherapy: results of a multicenter, randomized trial. Blood 2004;104(11 Part 2):10b.
    1. Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 2007;12(2):231‐42. - PubMed
Izuel‐Rami 2006 {published data only}
    1. Izuel‐Rami M, Garcia‐Erce JA, Cuenca J, Gomez‐Barrera M, Villar I, Rabanaque MJ. Recovery from postoperative anaemia after hip fracture replacement surgery. Is there a role for erythropoietin and intravenous iron?. Transfusion Alternatives in Transfusion Medicine 2006;8(1 Suppl):81.
Jacobs 2000 {published data only}
    1. Jacobs P, Wood L, Bird AR. Erythrocytes: better tolerance of iron polymaltose complex compared with ferrous sulphate in the treatment of anaemia. Hematology 2000;5(1):77‐83. - PubMed
Jakobsen 2013 {published data only}
    1. Jakobsen D, Wiesenthal M, Hartmann F, Dignass A, Weber‐Mangal S, Stein J. Safety and efficacy of bolus administered ferric carboxymaltose (500 mg) in the treatment of iron deficiency anaemia in IBD patients. Journal of Crohn's and Colitis 2013;7(Suppl 1):S162.
Kanakaraddi 1973 {published data only}
    1. Kanakaraddi VP, Hoskatti CG, Nadig VS, Patil CK, Maiya M. Comparative therapeutic study of T.D.I. and I.M. injections of iron dextran complex in anaemia. Journal of Association of Physicians of India 1973;21(10):849‐53. - PubMed
Kang 2006 {published data only}
    1. Kang SB, Kim SC, Kim YT. Phase IV randomized study on safety and usefulness of parenteral iron (iron sucrose, venoferrum C) in the management of preoperative anemia in patients with menorrhagia: preliminary data. XVIII FIGO World Congress of Gynecology and Obstetrics 2006;2:89.
Kim 2007 {published data only}
    1. Kim YT, Kim SW, Yoon BS, Cho HJ, Nahm EJ, Kim SH, et al. Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecologic Oncology 2007;105(1):199‐204. - PubMed
Kim 2009 {published data only}
    1. Kim YH, Chung HH, Kang SB, Kim SC, Kim YT. Safety and usefulness of intravenous iron sucrose in the management of preoperative anemia in patients with menorrhagia: a phase IV, open‐label, prospective, randomized study. Acta Haematologica 2009;121(1):37‐41. - PubMed
Kulnigg 2008 {published data only}
    1. Kulnigg S, Rumyantsev V, Stoinov S, Simanenkov V, Levchenko E, Karnafel W, et al. A novel intravenous iron formulation for treatment of anemia in IBD: the Ferinject randomized, controlled trial. Gastroenterology 2007;132(4 Suppl 2):A501‐2. - PubMed
    1. Kulnigg S, Rumyantsev V, Stoinov S, Simanenkov V, Levchenko E, Karnafel W, et al. A novel intravenous iron formulation for treatment of anemia in IBD: the Ferinject randomized, controlled trial. Zeitschrift fur Gastroenterologie 2007;44(A2):645‐6.
    1. Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. American Journal of Gastroenterology 2008;103(5):1182‐92. - PubMed
Langstaff 1993 {published data only}
    1. Langstaff RJ, Geisser P, Heil WG, Bowdler JM. Treatment of iron‐deficiency anaemia: a lower incidence of adverse effects with Ferrum Hausmann than ferrous sulphate. British Journal of Clinical Research 1993;4:191‐8.
Li 2005 {published data only}
    1. Li XX, Chen XL, Zhang MH, Wang YH, Da WM, Li JY. [A randomized controlled and multicenter clinical study of ferrous L‐threonate in treatment of iron deficiency anemia]. Zhonghua Nei Ke Aa Zhi [Chinese Journal of Internal Medicine] 2005;44(11):844‐7. - PubMed
Michalopoulou 2009 {published data only}
    1. Michalopoulou H, Vaitsis J, Massias S, Stamatis P. Effect of correction of anemia in severe congestive heart failure. Critical Care 2009;13:S168.
Mimura 2008 {published data only}
    1. Mimura EC, Bregano JW, Dichi JB, Gregorio EP, Dichi I. Comparison of ferrous sulfate and ferrous glycinate chelate for the treatment of iron deficiency anemia in gastrectomized patients. Nutrition 2008;24(7‐8):663‐8. - PubMed
NCT00199277 {published data only}
    1. Marti PP. Iron therapy in colo‐rectal neoplasm and iron deficiency anemia: intravenous iron sucrose versus oral ferrous sulphate. http://ClinicalTrials.gov/show/NCT00199277 2005:Accessed November 2014.
NCT00236951 {published data only}
    1. Trokars M. Intravenous (IV) iron vs. no iron as the treatment of anemia in cancer patients undergoing chemotherapy and erythropoietin therapy. http://ClinicalTrials.gov/show/NCT00236951 2010:Accessed November 2014.
NCT00482716 {published data only}
    1. Agrawal SG. Epoetin alfa or epoetin beta with or without iron infusion in treating anemia in patients with cancer. http://ClinicalTrials.gov/show/NCT00482716 2009:Accessed November 2014.
NCT00704028 {published data only}
    1. Tokars M. Safety and tolerability of ferric carboxymaltose (FCM) versus iron dextran in treating iron deficiency anemia. http://ClinicalTrials.gov/show/NCT00704028 2011:Accessed November 2014.
NCT00706667 {published data only}
    1. Theusinger O. Intravenous ferric carboxymaltose (Ferinject®) with or without erythropoietin in patients undergoing orthopaedic surgery. http://ClinicalTrials.gov/show/NCT00706667 2013:Accessed November 2014.
NCT00810030 {published data only}
    1. Gasche C. Ferinject for correction of anaemia in IBD patients, FER‐IBD‐COR. http://ClinicalTrials.gov/show/NCT00810030 2012:Accessed November 2014.
NCT00978575 {published data only}
    1. Vilstrup H. Iron substitution after upper gastro‐intestinal bleeding. http://ClinicalTrials.gov/show/NCT00978575 2013:Accessed November 2014.
NCT00982007 {published data only}
    1. Tokars M. Efficacy and safety of intravenous ferric carboxymaltose (FCM) in patients with iron deficiency anemia (IDA). http://ClinicalTrials.gov/show/NCT00982007 2013:Accessed November 2014.
NCT01017614 {published data only}
    1. Pharmacosmos A/S. Iron oligosaccharide in inflammatory bowel disease subjects with iron deficiency anaemia. http://ClinicalTrials.gov/show/NCT01017614 2012:Accessed November 2014.
NCT01100879 {published data only}
    1. Eirini K, Cushway T. Ferric carboxymaltose for treatment of anaemia of cancer in subjects with multiple myeloma receiving chemotherapy. http://ClinicalTrials.gov/show/NCT01100879 2011:Accessed November 2014.
NCT01101399 {published data only}
    1. Karlsson T, McNamara M. Ferric carboxymaltose in subjects with functional iron deficiency undergoing chemotherapy. http://ClinicalTrials.gov/show/NCT01101399 2012:Accessed November 2014.
NCT01114139 {published data only}
    1. AMAG Pharmaceuticals, Inc. A trial of ferumoxytol for the treatment of iron deficiency anemia. http://ClinicalTrials.gov/show/NCT01114139 2013:Accessed November 2014.
NCT01114204 {published data only}
    1. AMAG Pharmaceuticals, Inc. A trial comparing ferumoxytol with iron sucrose for the treatment of iron deficiency anemia. http://ClinicalTrials.gov/show/NCT01114204 2013:Accessed November 2014.
NCT01145638 {published data only}
    1. Thomsen LL. A study of intravenous iron isomaltoside 1000 (Monoferâ®) as monotherapy (without erythropoiesis stimulating agents) in comparison with oral iron sulfate in subjects with non‐myeloid malignancies associated with chemotherapy induced anaemia (CIA). http://ClinicalTrials.gov/show/NCT01145638 . Accessed November 2014.
NCT01160198 {published data only}
    1. GSK Clinical Trials. A study to demonstrate the efficacy and tolerability of ferrous bisglycinate chelate in iron deficiency anaemia and to compare these with those of ferrous ascorbate. http://ClinicalTrials.gov/show/NCT01160198 2012:Accessed November 2014.
NCT01180894 {published data only}
    1. Pieracci FM, Moore EE. IV iron for the anemia of traumatic critical illness. http://ClinicalTrials.gov/show/NCT01180894 2012:Accessed November 2014.
NCT01307007 {published data only}
    1. Tocars M. Hypophosphatemia with intravenous ferric carboxymaltose versus iron dextran in women with iron deficiency secondary to heavy uterine bleeding. http://ClinicalTrials.gov/show/NCT01307007 2013:Accessed November 2014.
NCT01309659 {published data only}
    1. Price E, Schrier S, Artiz A. Trial to evaluate the efficacy of intravenous iron in older adults with unexplained anemia. http://ClinicalTrials.gov/show/NCT01309659 2012:Accessed November 2014.
NCT01340872 {published data only}
    1. Harper C, Emery L. Safety and efficacy study of oral ferric iron to treat iron deficiency anaemia in quiescent ulcerative colitis (AEGIS‐1). http://ClinicalTrials.gov/show/NCT01340872 2011:Accessed November 2014.
NCT01352221 {published data only}
    1. Harper C, Emery L. Safety and efficacy study of oral ferric iron to treat iron deficiency anaemia in quiescent Crohn's disease (AEGIS‐2). http://ClinicalTrials.gov/show/NCT01352221 2011:Accessed November 2014.
NCT01425463 {published data only}
    1. UCB, Inc. A double‐blind, double‐dummy, parallel, active‐controlled, randomized and multi‐center trial to investigate efficacy and safety in subjects with iron deficiency anemia for ferrous (II) glycine sulphate complex versus polyferose capsules therapy. http://ClinicalTrials.gov/show/NCT01425463 2013:Accessed November 2014.
NCT01428843 {published data only}
    1. Savoye G, Colombel JF. Comparison of ferrisat vs placebo in anemia associated to inflammatory bowel disease during anti‐TNF therapy. http://ClinicalTrials.gov/show/NCT01428843 2012:Accessed November 2014.
NCT01690585 {published data only}
    1. Blot J. Efficacy of parenteral iron supplementation after gastrointestinal bleeding in subjects over 65. http://ClinicalTrials.gov/show/NCT01690585 2013:Accessed November 2014.
NCT01701310 {published data only}
    1. Keeler B, Ahceson AG. IVICA: intravenous iron in colorectal cancer associated anaemia. http://ClinicalTrials.gov/show/NCT01701310 2013:Accessed November 2014.
NCT01725789 {published data only}
    1. Kim YW. Ferinject® assessment in gastrectomy patients with acute isovolemic anemia (FAIRY). http://ClinicalTrials.gov/show/NCT01725789 2013:Accessed November 2014.
NCT01733979 {published data only}
    1. Chae SW. Efficacy and safety of heme‐iron polypeptide on improvement of anemia. http://ClinicalTrials.gov/show/NCT01733979 2012:Accessed November 2014.
NCT01837082 {published data only}
    1. Karakas M. Iron in congestive heart failure. http://ClinicalTrials.gov/show/NCT01837082 2013:Accessed November 2014.
NCT01857011 {published data only}
    1. Montano‐Pedroso JC. Iron supplementation for acute anemia after postbariatric abdominoplasty. http://ClinicalTrials.gov/show/NCT01857011 2013:Accessed November 2014.
NCT01927328 {published data only}
    1. Keeler B, Acheson AG. Iron replacement in oesophagogastric neoplasia. http://ClinicalTrials.gov/show/NCT01927328 2013:Accessed November 2014.
NCT01950247 {published data only}
    1. Koch T, Trokars M. Trial to evaluate the utility of serum hepcidin levels to predict response to oral or iv iron and to compare safety, effect on quality of life, and resource utilization of injectafer vs. intravenous standard of care for the treatment of iron deficiency anemia (IDA) in an infusion center setting. http://ClinicalTrials.gov/show/NCT01950247 2013:Accessed November 2014.
Okonko 2008 {published data only}
    1. Okonko D, Greszlo A, Witkowski T, Mandal A, Slater R, Roughton M, et al. Effect of intravenous iron sucrose on exercise tolerance in anaemic and nonanaemic patients with symptomatic chronic heart failure and iron deficiency (ferric‐HF): a randomised, controlled, observer‐blinded trial. Heart 2007;93(Suppl 1):A41. - PubMed
    1. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Foldes G, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and non‐anemic patients with symptomatic chronic heart failure and iron deficiency: a randomised, controlled, observer‐blinded trial (FERRIC‐HF). Circulation 2006;114(18 Suppl S):407. - PubMed
    1. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC‐HF: a randomized, controlled, observer‐blinded trial. Journal of the American College of Cardiology 2008;51(2):103‐12. - PubMed
    1. Okonko DO, Grzeslo A, Witkowski T, Missouris CG, Banasiak W, Poole‐Wilson PA, et al. Effect of intravenous iron sucrose on exercise tolerance in anaemic and non‐anaemic iron deficient patients with chronic heart failure: a randomised, controlled, observer‐blinded trial (FERRIC‐HF). European Heart Journal 2006;27(Suppl 1):167.
Olijhoek 2001 {published data only}
    1. Olijhoek G, Megens JGN, Musto P, Nogarin L, Gassmann‐Mayer C, Vercammen E, et al. Role of oral versus IV iron supplementation in the erythropoietic response to rHuEPO: a randomized, placebo‐controlled trial. Transfusion 2001;41(7):957‐63. - PubMed
Oliver 2010 {published data only}
    1. Oliver A, Sierra P, Noe L, Monllau V, Ortiz JC. Efficacy of post‐operative intravenous iron in elective major urological surgery. Transfusion Alternatives in Transfusion Medicine 2010;11(Suppl S2):33.
Pedrazzoli 1988 {published data only}
    1. Pedrazzoli P, Scotti A, Farina D. Comparison trial of iron succinylprotein complex or iron gluconate complex in the treatment of iron deficiency anemia. Clinical Therapeutics 1988;10(4):414‐20. - PubMed
Pedrazzoli 2008 {published data only}
    1. Pedrazzoli P, Farris A, Prete S, Gaizo F, Ferrari D, Bianchessi C, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy‐related anemia without iron deficiency treated with darbepoetin alpha. Journal of Clinical Oncology 2008;26(10):1619‐25. - PubMed
    1. Siena S, Farris A, Prete S, Gaizo F, Ferrari D, Bianchessi C, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy‐related anemia without iron deficiency treated with darbepoetin alfa. Annals of Oncology 2007;18(Suppl 11):87‐8. - PubMed
Prasad 2009 {published data only}
    1. Prasad N, Rajamani V, Hullin D, Murray JM. Post‐operative anaemia in femoral neck fracture patients: does it need treatment? A single blinded prospective randomised controlled trial. Injury 2009;40(10):1073‐6. - PubMed
Prassler 1998 {published data only}
    1. Prassler R, Deppe H, Huchzermeyer H. Value of iron supplementation in gastrointestinal bleeding. Leber Magen Darm 1998;28(1):21‐3.
Roe 1968 {published data only}
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NCT01692418 {published data only}
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