Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial

Akshay Shah; Mae Chester-Jones; Susan J Dutton; Ioana R Marian; Vicki S Barber; David M Griffith; Jo Singleton; Katherine Wray; Tim James; Hal Drakesmith; Peter A Robbins; Matthew C Frise; J Duncan Young; Timothy S Walsh; Stuart R McKechnie; Simon J Stanworth; INTACT Investigators

doi:10.1016/j.bja.2021.11.010

Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial

Br J Anaesth. 2022 Feb;128(2):272-282. doi: 10.1016/j.bja.2021.11.010. Epub 2021 Dec 3.

Authors

Akshay Shah¹, Mae Chester-Jones², Susan J Dutton², Ioana R Marian², Vicki S Barber², David M Griffith³, Jo Singleton⁴, Katherine Wray⁵, Tim James⁶, Hal Drakesmith⁷, Peter A Robbins⁸, Matthew C Frise⁹, J Duncan Young¹⁰, Timothy S Walsh¹¹, Stuart R McKechnie¹², Simon J Stanworth¹³; INTACT Investigators

Collaborators

INTACT Investigators:
Paula Hutton¹⁴, Archana Bashyal¹⁴, George Chapman¹⁴, Killian Donovan¹⁴, Christie James¹⁴, Nicola Rea¹⁵, Sarah Clark¹⁵, Lucy Barclay¹⁵, Kate Priestley¹⁵, David Hope¹⁵, Corrienne McCulloch¹⁵, Nicola Jacques¹⁶, Shauna Bartley¹⁶, Parminder Bhachu¹⁶, Joanna Black, Emma Haines, Lucy Eldridge, Quentin Hill, Andrew Walden, Toby Richards

Affiliations

¹ Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Adult Intensive Care Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: akshay.shah@linacre.ox.ac.uk.
² Oxford Clinical Trials Research Unit (OCTRU), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
³ Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Edinburgh, UK; Deanery of Molecular, Genetic and Population Health Sciences and University of Edinburgh, Edinburgh, UK.
⁴ Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Edinburgh, UK.
⁵ MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford, UK.
⁶ Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁷ MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford, UK; Haematology Theme, NIHR Oxford Biomedical Research Centre, Oxford, UK.
⁸ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
⁹ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Intensive Care Unit, Royal Berkshire Hospitals NHS Foundation Trust, Reading, UK.
¹⁰ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹¹ Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Edinburgh, UK; Usher Institute for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
¹² Adult Intensive Care Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹³ Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Haematology Theme, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹⁴ Oxford University Hospitals NHS Foundation Trust, UK.
¹⁵ Edinburgh Royal Infirmary NHS Lothian, UK.
¹⁶ Royal Berkshire Hospital, UK.

PMID: 34872717
DOI: 10.1016/j.bja.2021.11.010

Abstract

Background: Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear.

Methods: We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.v. or usual care in patients being discharged from the ICU with moderate or severe anaemia (haemoglobin ≤100 g L^-1). We collected data on feasibility (recruitment, randomisation, follow-up), biological efficacy, and clinical outcomes.

Results: Ninety-eight participants were randomly allocated (49 in each arm). The overall recruitment rate was 34% with 6.5 participants recruited on average per month. Forty-seven of 49 (96%) participants received the intervention. Patient-reported outcome measures were available for 79/93 (85%) survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs 106.7 [14.9] g L^-1) and 90 days (130.5 [15.1] vs 122.7 [17.3] g L^-1), adjusted mean difference (10.98 g L^-1; 95% confidence interval [CI], 4.96-17.01; P<0.001) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the i.v. iron group (7/40 vs 15/39; risk ratio=0.46; 95% CI, 0.21-0.99; P=0.037). The median (inter-quartile range) post-ICU hospital stay was shorter in the i.v. iron group but did not reach statistical significance (5.0 [3.0-13.0] vs 9.0 [5.0-16.0] days, P=0.15).

Conclusion: A large, multicentre RCT of i.v. iron to treat anaemia in survivors of critical illness appears feasible and is necessary to determine the effects on patient-centred outcomes.

Clinical trial registration: ISRCTN13721808 (www.isrctn.com).

Keywords: anaemia; critical care; intravenous iron; outcomes; randomised controlled trial.

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial

MeSH terms

Administration, Intravenous
Adolescent
Adult
Aged
Aged, 80 and over
Anemia / drug therapy*
Critical Care
Feasibility Studies
Female
Ferric Compounds / administration & dosage*
Follow-Up Studies
Hematinics / administration & dosage*
Hemoglobins / analysis
Humans
Length of Stay
Male
Maltose / administration & dosage
Maltose / analogs & derivatives*
Middle Aged
Patient Readmission / statistics & numerical data
Patient Reported Outcome Measures
Young Adult

Substances

Ferric Compounds
Hematinics
Hemoglobins
ferric carboxymaltose
Maltose