Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial)

Robert Kong; Nevil Hutchinson; Andrew Hill; Fiona Ingoldby; Nicola Skipper; Christopher Jones; Stephen Bremner; Chloe Bruce; Juliet Wright; Michael Lewis; Stanton Newman; Timothy Chevassut; David Hildick-Smith

doi:10.1016/j.bja.2022.01.034

Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial)

Br J Anaesth. 2022 May;128(5):796-805. doi: 10.1016/j.bja.2022.01.034. Epub 2022 Mar 5.

Authors

Affiliations

¹ Department of Anaesthesia, Royal Sussex County Hospital, Brighton, UK. Electronic address: robert.kong@nhs.net.
² Department of Anaesthesia, Royal Sussex County Hospital, Brighton, UK.
³ University Hospitals Sussex NHS Foundation Trust, Clinical Research Facility, Cardiac Research, Brighton, UK.
⁴ Brighton and Sussex Clinical Trials Unit, Brighton & Sussex Medical School, University of Sussex, Brighton, UK.
⁵ Brighton and Sussex Medical School, Brighton, UK.
⁶ Department of Cardiac Surgery, Royal Sussex County Hospital, Brighton, UK.
⁷ School of Health Sciences, University of London, London, UK.
⁸ Department of Haematology, Royal Sussex County Hospital, Brighton, UK.
⁹ Department of Cardiology, Royal Sussex County Hospital, Brighton, UK.

PMID: 35256150
DOI: 10.1016/j.bja.2022.01.034

Abstract

Background: Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined.

Methods: We conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100-130 g L^-1) with iron deficiency (serum ferritin <100 μg L^-1 or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 μg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death.

Results: The odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15-0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L^-1 (95% CI, 6.8-12.2; P<0.001).

Conclusions: In patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate.

Clinical trial registration: ISRCTN Number: 41421863; EUDRACT number: 2011-003695-36.

Keywords: anaemia; cardiac surgery; darbepoetin; intravenous iron; iron deficiency; preoperative; transfusion.

Publication types

Randomized Controlled Trial

MeSH terms

Anemia* / drug therapy
Anemia* / etiology
Anemia, Iron-Deficiency* / drug therapy
Cardiac Surgical Procedures* / adverse effects
Disaccharides
Erythropoiesis
Ferric Compounds
Hematinics* / therapeutic use
Hemoglobins
Hospital Mortality
Humans
Iron / therapeutic use

Substances

Disaccharides
Ferric Compounds
Hematinics
Hemoglobins
ferric derisomaltose
Iron