Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial.

BACKGROUND: Despite increasing efforts in perioperative management, postoperative iron deficiency anaemia persists, and few data are available about the management of this condition. In this study, we aimed to determine whether giving postoperative intravenous iron (in the form of ferric carboxymaltose) improved iron stores, haemoglobin concentrations, and outcomes following surgery.

METHODS: We did a prospective, open-label, randomised, controlled study of patients at two centres (a general hospital and a private health-care centre) in Tasmania, Australia, undergoing elective surgery with functional iron deficiency anaemia (haemoglobin 70-120 g/L and ferritin ≤100 μg/L or iron saturation ≤20%), measured at day 1 postoperatively. Consecutive routine elective surgical patients who were having major orthopaedic surgery, abdominal, and genitourinary surgery, and other surgeries were recruited. Via computer-generated randomisation, patients were randomly assigned (1:1) to either a single dose of intravenous 1000 mg ferric carboxymaltose (intervention group) or standard care, consisting of observation (control group). The primary endpoints were changes in haemoglobin concentrations and iron stores at 4 weeks postoperatively, and the number of transfused units of blood required postoperatively until discharge. Analyses were done on an intention-to-treat basis. This trial is registered with the Australian New Zealand Clinical Trials Registry and the WHO International Clinical Trials Registry platform (number ACTRN12614001261606).

FINDINGS: Between Dec 17, 2014, and May 7, 2015, we recruited 201 eligible patients, assigning 103 to intravenous ferric carboxymaltose and 98 to standard care only. Baseline mean haemoglobin was 105·5 g/L (SD 13·8) in the standard care group versus 106·2 g/L (11·9) in the ferric carboxymaltose group, improving at 4 weeks to 121·5 g/L (SD 14·5) in the standard group and 130·1 g/L (11·3) in the ferric carboxymaltose group (mean difference of 7·84 g/L, 95% CI 3·79-11·9; p<0·0001 in favour of the ferric carboxymaltose group). Significant improvements in serum iron (5·36 μmol/L, 95% CI 3·62-7·09; p<0·0001), iron saturation (11·40%, 95% CI 8·33-14·50; p<0·0001), and serum ferritin concentrations (468 μg/L, 95% CI 355-582; p<0·0001) were also noted in the ferric carboxymaltose group at 4 weeks compared with standard care, although no differences were noted in transferrin concentrations (0·06 g/L, 95% CI -0·97 to 1·09; p=0·62). Fewer transfused blood units were given in the ferric carboxymaltose group (to one of 103 patients [<1%]) than in the standard care group (to five of 98 patients [5%]; incidence rate ratio 0·10; 95% CI 0·01-0·85; p=0·035). No adverse events were observed with ferric carboxymaltose treatment.

INTERPRETATION: Postoperative intravenous ferric carboxymaltose is a feasible and pragmatic management approach in surgical patients with functional iron deficiency anaemia. Our study suggests that patient blood management guidelines should be updated, incorporating the use of postoperative intravenous iron infusion to optimise patient outcomes. Further trials to assess our approach are warranted.

FUNDING: Launceston General Hospital, Launceston, TAS, Australia, in affiliation with the University of Tasmania, TAS, Australia.