HiFIT Study : Hip Fracture: Iron and Tranexamic Acid (HiFIT)

HiFIT Study: Interest of Intravenous Iron and Tranexamic Acid to Reduce Transfusion in Hip Fracture Patients

1year inclusion hold due to PV new fact (Monofer hold for risk revaluation) DSMB Interim analysis : 1treatment with important transfusion risk reduction/inclusions issues (COVID)/sites change of practice if study continue=>stop inclusions

Fractures of the upper end of the femur, called commonly "Hip fractures" are very common, with an incidence of approximately 1.6 million cases per year worldwide. This high incidence is anticipated to grow rapidly in the next decades, driven by population aging. Anemia is very frequent on admission for hip fracture, concerning up to 45% of the patients, with a mean hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood losses, secondary to the fracture itself and surgery are responsible for a high rate of blood transfusion (approximately 40-50% of the patients). However, both anemia and blood transfusion are associated with poor outcome, including increased mortality, length of stay, infection rate etc. In addition, blood is a scarce and expensive resource and its use should be limited as much as possible. There is therefore a need to treat this anemia and/or to prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed. Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous iron was able to reduce blood transfusion (i.e. the number of patients transfused and the number of units per patient). Another way to reduce blood transfusion would be to reduce perioperative bleeding. Tranexamic acid has proven to be efficient for this purpose both in trauma patients and in elective surgery patients.The interest for perioperative blood management has recently increased thanks to better recognition of the adverse effects of blood transfusion, better understanding of iron metabolism, new intravenous iron drugs and a renewed interest in former medications (i.e. tranexamic acid). HiFIT study therefore propose a 2X2 factorial design for this study in order to answer questions vis-à-vis the interest of iron and tranexamic acid to reduce blood transfusion in hip fracture patients.

Fractures of the upper end of the femur, called commonly "Hip fractures"are very common, with an incidence of approximately 1.6 million cases per year worldwide. This high incidence is anticipated to grow rapidly in the next decades, driven by population aging. Anemia is very frequent on admission for hip fracture, concerning up to 45% of the patients, with a mean hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood losses, secondary to the fracture itself and surgery are responsible for a high rate of blood transfusion (approximately 40-50% of the patients). However, both anemia and blood transfusion are associated with poor outcome, including increased mortality, length of stay, infection rate etc. In addition, blood is a scarce and expensive resource and its use should be limited as much as possible. There is therefore a need to treat this anemia and/or to prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed. Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous iron was able to reduce blood transfusion (i.e. the number of patients transfused and the number of units per patient). Indeed, a pooled analysis of 5 studies including 1,361 patients suggests that intravenous iron could reduce perioperative transfusion in hip fracture patients. However, there is no definitive data. Another way to reduce blood transfusion would be to reduce perioperative bleeding. Tranexamic acid has proven to be efficient for this purpose both in trauma patients and in elective surgery patients. However, there are only two randomized studies investigating the interest of tranexamic acid in hip fractures, and they are not conclusive probably owing to a lack of power. In addition, use of intravenous tranexamic acid could be limited in this population of frail patients and topical use of tranexamic acid, notably to prevent the intraoperative bleeding, appear to be an accurate and sure alternative. Although hip fracture is a very frequent pathology, with a high burden of care, few data are available that focus on the management of perioperative anemia in this context. The interest for perioperative blood management has recently increased thanks to better recognition of the adverse effects of blood transfusion, better understanding of iron metabolism, new intravenous iron drugs and a renewed interest in former medications (i.e. tranexamic acid). hiFIT study therefore propose a 2X2 factorial design for this study in order to answer questions vis-à-vis the interest of iron and tranexamic acid to reduce blood transfusion in hip fracture patients.

The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid

Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment

placebo of Iron Isomaltoside 1000 correspond to a saline solution. Blinding procedure will be put in place for the administration of this treatment

Proportion of patients who received a blood transfusion during the month following surgery (including fresh frozen plasma and platelets)

Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units

Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units

Till postoperative Day3, first week posteratively,and till hospital discharge (or one month if patients still hospitalised)

Perioperative blood loss (estimated according to a formula based on hematocrit variation): (HtD0 - HtD3)*TBV + number of RPBC transfused unit x 200 ml. Ht = Haematocrit, TBV = total blood volume (70 mL/kg in men and 65 mL/kg in women)

Proportion of patients with Iron deficiency (defined as a ferritin < 100 ng/ml or < 300 ng/ml together with transferrin saturation <20%), measurement of ferritin and transferrin saturation

Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications

Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications

Muscular fatigability between the first attempt and the third attempt of the Hand Grip Strength test (variation of the maximum strength measured at the first and the third atempt)

Inclusion Criteria: Age ≥ 18 years, Osteoporotic Fractures of the upper end of the femur requiring surgical repair. Preoperative hemoglobin between 9.5 and 13 g/dl. Patient or relative signed informed consent or inclusion thanks to urgent inclusion procedure Exclusion Criteria: Bone marrow disease or ongoing treatment (such as chemotherapy), which could interfere with bone marrow erythropoiesis, Known allergy or counter-indication to iron and/or to tranexamic acid, Uncontrolled arterial hypertension, Recent iron infusion (within one week), Blood transfusion within one week before inclusion or preoperative blood transfusion already scheduled, Any patient who cannot be transfused or has refused consent for a blood transfusion, Bedridden or very dependent patient (equivalent to GIR 1 or 2 class). Non-affiliation to French health care coverage, Adult patient protected under the law (guardianship), Pregnancy.

Lasocki S, Bruckert V, Campfort M, Leger M, Rineau E. Restrictive transfusion targets the heart now! Insight from the REALITY study. Anaesth Crit Care Pain Med. 2021 Apr;40(2):100854. doi: 10.1016/j.accpm.2021.100854. Epub 2021 Mar 27. No abstract available.

Lasocki S, Loupec T, Parot-Schinkel E, Vielle B, Danguy des Deserts M, Roquilly A, Lahlou-Casulli M, Collange V, Desebbe O, Duchalais A, Drugeon B, Bouzat P, Garrigue D, Mounet B, Hamard F, David JS, Leger M, Rineau E; HiFIT Study Group. Study protocol for a multicentre, 2x2 factorial, randomised, controlled trial evaluating the interest of intravenous iron and tranexamic acid to reduce blood transfusion in hip fracture patients (the HiFIT study). BMJ Open. 2021 Jan 17;11(1):e040273. doi: 10.1136/bmjopen-2020-040273.