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Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial

A randomized trial of IV iron in critical illness

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Abstract

Purpose

Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain.

Methods

The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge.

Results

Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43–1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97–115) vs. 100 g/L (IQR 89–111), P = 0.02]. There was no significant difference between the groups in any safety outcome.

Conclusions

In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge.

The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842.

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Acknowledgments

E.L. is a PhD candidate at the University of Western Australia and this work is submitted in partial fulfilment of the requirement for the Ph.D. The IRONMAN RCT is part of the Blood – CRE, Centre of Research Excellence for Patient Blood Management in Critical Illness and Trauma

Author information

Authors and Affiliations

  1. Intensive Care Unit, Fiona Stanley Hospital, Perth, WA, 6150, Australia

    Edward Litton, Janet Ferrier, Bart De Keulenaer & Simon Towler

  2. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, 6009, Australia

    Edward Litton & Steve Webb

  3. Intensive Care Unit, Sir Charles Gardner Hospital, Perth, WA, 6009, Australia

    Stuart Baker

  4. School of Pathology and Laboratory Medicine, University of Australia, Perth, WA, 6009, Australia

    Wendy N. Erber

  5. Center for Population Health Research, Curtin University, Perth, WA, 6102, Australia

    Shannon Farmer & Axel Hofmann

  6. Western Health, Melbourne, VIC, Australia

    Craig French

  7. University of Melbourne, Melbourne, VIC, Australia

    Craig French

  8. Separation Science and Metabolomics Laboratory, Murdoch University, Perth, WA, Australia

    Joel Gummer & Robert Trengove

  9. Intensive Care Unit, Joondalup Health Campus, Perth, WA, Australia

    David Hawkins

  10. Centre of Research Excellence for Patient Blood Management in Critical Illness and Trauma, Monash University, Melbourne, VIC, Australia

    Alisa Higgins

  11. Intensive Care Unit, Royal Perth Hospital, Perth, WA, 6000, Australia

    Julie McMorrow & Steve Webb

  12. University College London, London, UK

    Toby Richards

  13. CTEC School of Surgery, Faculty of Medicine Dentistry and Health Sciences, The University of Western Australia, Perth, WA, Australia

    Shannon Farmer

  14. Institute of Anaesthesiology, University Hospital, Zurich, Switzerland

    Axel Hofmann

  15. Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, WA, 6150, Australia

    John K. Olynyk

Authors
  1. Edward Litton
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  2. Stuart Baker
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  3. Wendy N. Erber
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  4. Shannon Farmer
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  5. Janet Ferrier
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  7. Joel Gummer
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  8. David Hawkins
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  9. Alisa Higgins
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  10. Axel Hofmann
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  11. Bart De Keulenaer
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  12. Julie McMorrow
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  14. Toby Richards
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  15. Simon Towler
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  16. Robert Trengove
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  17. Steve Webb
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Consortia

The IRONMAN Investigators

The Australian and New Zealand Intensive Care Society Clinical Trials Group

Corresponding author

Correspondence to Edward Litton.

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Conflicts of interest

Dr. Richards reports grants from the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA), the Australian National Health and Medical Research Council (NHMRC) and the UK National Institute of Academic Anaesthesia (NIAA)/British Journal of Anaesthesia (BJA)/Association of Cardiothoracic Anaesthetists (ACTA)/Vascular Anaesthesia Society of Great Britain and Ireland (VASGBI); grants, personal fees and non-financial support from Pharmocosmos, Vifor Pharma, Acelity and the Stroke Association; grants from Mason Medical Research Foundation and University College Hospital (UCH) League of Friends; grants and non-financial support from Libresse/Bodyform, outside the submitted work. TR is a regular speaker at national and international conferences on anaemia, blood transfusion, wound healing and vascular diseases for which he has received expenses for travel, accommodation and sundries. TR is a director of The Iron Clinic Ltd and director of Veincare London Ltd. TR is also the vascular lead for 18-Week Wait Ltd. Shannon Farmer reports personal fees from Thieme Stuttgart, Germany, and Elsevier Science USA, non-financial support from the National Blood Authority (Australia), the Medical Society for Blood Management and non-financial support from The Health Round Table, outside the submitted work. Dr. Hofmann reports personal fees from Vifor Pharma AG and TEM International GmbH, outside the submitted work. The other authors declare no conflict of interest.

Additional information

A list of additional IRONMAN site investigators and research coordinators is provided in the electronic supplementary material.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 405 kb)

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The IRONMAN Investigators., Litton, E., Baker, S. et al. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. Intensive Care Med 42, 1715–1722 (2016). https://doi.org/10.1007/s00134-016-4465-6

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  • DOI: https://doi.org/10.1007/s00134-016-4465-6

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