HiFIT Study : Hip Fracture: Iron and Tranexamic Acid

University Hospital, Angers

Status and phase: Terminated; Phase 3

Conditions: Anemia; Hip Fractures Pathologic

Treatments: Drug: Placebos iron isomaltoside 1000; Drug: Iron Isomaltoside 1000; Drug: Tranexamic Acid; Drug: Placebos tranexamic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT02972294

49RC16_0014

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 419 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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419 participants in 4 patient groups

TXA + IIM

Experimental group

Description:

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

Treatment:

Drug: Tranexamic Acid

Drug: Iron Isomaltoside 1000

Placebo TXA + IIM

Experimental group

Description:

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

Treatment:

Drug: Placebos tranexamic acid

Drug: Iron Isomaltoside 1000

TXA + Placebo IIM

Experimental group

Description:

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

Treatment:

Drug: Tranexamic Acid

Drug: Placebos iron isomaltoside 1000

Placebo TXA + Placebo IIM

Experimental group

Description:

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

Treatment:

Drug: Placebos tranexamic acid

Drug: Placebos iron isomaltoside 1000