Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial

Abstract

Background: Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes.

Methods: In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10-42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants.

Findings: Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78-1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68-1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints.

Interpretation: Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10-42 days before elective major abdominal surgery.

Funding: UK National Institute of Health Research Health Technology Assessment Program.

Figure 1

Trial profile ITT=intention-to-treat. IV=intravenous. *Patient had blood transfusion before withdrawal or loss to follow-up and is therefore included in analysis of the coprimary endpoints.

Figure 2

Mean haemoglobin concentrations of the trial participants by randomised treatment group Error bars show 95% CI. BL=baseline prerandomised treatment. OP=day of operation before surgery. D=day post operation (eg, D2–3=day 2 or 3 post operation). D2–3, D4–5, D6–7, and D14 measurements are only available for patients still hospitalised at that time. IV=intravenous.