Clinical trial NCT02972294: HiFIT Study : Hip Fracture: Iron and Tranexamic Acid
Official title: HiFIT Study: Interest of Intravenous Iron and Tranexamic Acid to Reduce Transfusion in Hip Fracture Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hip Fractures Pathologic
Anemia
Keywords: iron isomaltoside
tranexamic acid
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2016-11-23
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients who received a blood transfusion during their hospital stay following surgery
timeFrame: From the day of surgery until hospital discharge (or until day 30 if patient is still hospitalized).
Secondary outcomes:
measure: Proportion of patients who received a blood transfusion after surgery
timeFrame: From the day of surgery until Day 3, Day 7 and Day 30 post surgery.
measure: Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units
timeFrame: Till postoperative Day3, first week posteratively,and till hospital discharge (or one month if patients still hospitalised)
measure: Hemoglobin concentration
timeFrame: At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30.
measure: Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men)
timeFrame: At inclusion and on days 3, 7, hospital discharge (if it happens before Day 30) and 30.
measure: Reticulocytes count
timeFrame: On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery
measure: Perioperative blood loss (estimated according to a formula based on hematocrit variation).
timeFrame: During surgery
measure: Post operative Iron deficiency rate
timeFrame: On Day 7 (or hospital discharge if it happens first) and Day 30.
measure: Number of hospitalization days
timeFrame: On Day 30 and Day 90 following surgery.
measure: Proportion of patients at home
timeFrame: On Day 30 and Day 90.
measure: Proportion of patients able to walk a distance of ten feet without assistance
timeFrame: On Day 30 and Day 90
measure: Variation of quality of life
timeFrame: From inclusion to Day 30 and Day 90
measure: Variation of perceived quality of life
timeFrame: From inclusion to Day 7 (or hospital discharge if it happens first) and Day 90.
measure: Variation of IADL test
timeFrame: From inclusion to Day 90.
measure: Death rate from all causes
timeFrame: From inclusion to Day 90
measure: Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications
timeFrame: From inclusion to Day 90
Other outcomes:
measure: Strength assessed by the Hand Grip Strength test
timeFrame: On day 7 (or hospital discharge if it happens first)
measure: Muscular fatigability assessed by the Hand Grip Strength test
timeFrame: On day 7 (or hospital discharge if it happens first)
measure: Level of locomotion and balance assessed by the Timed " Up and Go " test.
timeFrame: On day 7 (or hospital discharge if it happens first)
Locations:
city: Angers
country: France
facility: CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION
city: Angers
country: France
facility: Clinique de L'Anjou- Anesthesie Reanimation
city: Brest
country: France
facility: HIA Clermont-Tonnerre
city: Grenoble
country: France
facility: Chu Grenoble - Departement D'Anesthesie Reanimation
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Hospices Civils Lyon
city: Lyon
country: France
facility: Ramsay Santé, Clinique de la Sauvegarde
city: Montpellier
country: France
facility: Chu Montpellier - Departement D'Anesthesie Reanimation
city: Nantes
country: France
facility: Chu Nantes- Service de Reanimation Chirurgicale
city: Poitiers
country: France
facility: Chu Poitiers - Service D'Anesthesie Reanimation
city: Rennes
country: France
facility: Chu Rennes - Service D'Anesthesie Reanimation
city: Villeurbanne
country: France
facility: Medipôle
Study officials:
affiliation: UNIVERSITE HOSPITAL, ANGERS
name: Sigismond SL Lasocki, PU-PH
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.