Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 INM - Institut des Neurosciences de Montpellier
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
6 MLV - Médipôle Lyon-Villeurbanne
7 Service d'anesthésie et réanimation chirurgicale [Nantes]
8 Hôpital d'Instruction des Armées Clermont Tonnerre
9 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
10 Clinique de la Sauvegarde [Lyon]
11 UFR Santé [Poitiers] - Université de Poitiers – UFR Santé [Faculté de Médecine et de Pharmacie]
12 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
13 PHAR2 [Poitiers] - Pharmacologie des anti-infectieux et antibiorésistance [U 1070]
14 UGA - Université Grenoble Alpes
15 GIN - [GIN] Grenoble Institut des Neurosciences
16 RESHAPE - Inserm U1290 - UCBL1 - Research on Healthcare Performance
17 UM - Université de Montpellier
18 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
19 Penn State - Pennsylvania State University
20 Hôpital Saint Eloi
21 Hôpital Lapeyronie [CHU Montpellier]
22 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
23 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
24 OSS - Oncogenesis, Stress, Signaling
25 CIC - Centre d'Investigation Clinique [Rennes]
26 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
27 TIMC-GREPI - Groupe de Recherche et d’Étude du Processus Inflammatoire
28 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
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Résumé
Background: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery.
Methods: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients.
This study is registered on ClinicalTrials.gov (NCT02972294)
Findings: Of 413 patients (51–104 years old, median [IQR] 86 [78–91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27−0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50−1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54−1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups.
Interpretation: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5–13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it.