HiFIT Study : Hip Fracture: Iron and Tranexamic Acid

Anemia Clinical Trial

— HiFIT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02972294
• Other study ID #: 49RC16_0014
• Status: Terminated
• Phase: Phase 3
• Start date: March 31, 2017
• Est. completion date: September 16, 2021

Study information

• Verified date: July 2022
• Source: University Hospital, Angers
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 419
• Est. completion date: September 16, 2021
• Est. primary completion date: September 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Fractures, Bone
• Hip Fractures
• Hip Fractures Pathologic

Intervention

Drug:
• Iron Isomaltoside 1000
Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment
• Tranexamic Acid
Tranexamic acid will be use.
• Placebos iron isomaltoside 1000
placebo of Iron Isomaltoside 1000 correspond to a saline solution. Blinding procedure will be put in place for the administration of this treatment
• Placebos tranexamic acid
placebo of tranexamic acid correspond to a saline solution.

Locations

Country	Name	City	State
France	CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION	Angers
France	Clinique de L'Anjou- Anesthesie Reanimation	Angers
France	HIA Clermont-Tonnerre	Brest
France	Chu Grenoble - Departement D'Anesthesie Reanimation	Grenoble
France	CHD Vendée	La Roche-sur-Yon
France	CHU Lille	Lille
France	Hospices Civils Lyon	Lyon
France	Ramsay Santé, Clinique de la Sauvegarde	Lyon
France	Chu Montpellier - Departement D'Anesthesie Reanimation	Montpellier
France	Chu Nantes- Service de Reanimation Chirurgicale	Nantes
France	Chu Poitiers - Service D'Anesthesie Reanimation	Poitiers
France	Chu Rennes - Service D'Anesthesie Reanimation	Rennes
France	Medipôle	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Strength assessed by the Hand Grip Strength test	Maximum strength of the hand and forearm muscles assessed by the Hand Grip Strength test	On day 7 (or hospital discharge if it happens first)
Other	Muscular fatigability assessed by the Hand Grip Strength test	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)	On day 7 (or hospital discharge if it happens first)
Other	Level of locomotion and balance assessed by the Timed " Up and Go " test.	Level of locomotion and balance assessed by the Timed " Up and Go " test,	On day 7 (or hospital discharge if it happens first)
Primary	Proportion of patients who received a blood transfusion during their hospital stay following surgery	Proportion of patients who received a blood transfusion during their hospital stay following surgery	From the day of surgery until hospital discharge (or until day 30 if patient is still hospitalized).
Secondary	Proportion of patients who received a blood transfusion after surgery	Proportion of patients who received a blood transfusion during the month following surgery (including fresh frozen plasma and platelets)	From the day of surgery until Day 3, Day 7 and Day 30 post surgery.
Secondary	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)
Secondary	Hemoglobin concentration	Hemoglobin concentration	At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30.
Secondary	Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men)	Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men)	At inclusion and on days 3, 7, hospital discharge (if it happens before Day 30) and 30.
Secondary	Reticulocytes count	Reticulocytes count	On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery
Secondary	Perioperative blood loss (estimated according to a formula based on hematocrit variation).	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)	During surgery
Secondary	Post operative Iron deficiency rate	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	On Day 7 (or hospital discharge if it happens first) and Day 30.
Secondary	Number of hospitalization days	Number of hospitalization days	On Day 30 and Day 90 following surgery.
Secondary	Proportion of patients at home	Proportion of patients returned at home (or at their previous place of living)	On Day 30 and Day 90.
Secondary	Proportion of patients able to walk a distance of ten feet without assistance	Proportion of patients able to walk a distance of ten feet without assistance	On Day 30 and Day 90
Secondary	Variation of quality of life	Variation of EQ-5D score	From inclusion to Day 30 and Day 90
Secondary	Variation of perceived quality of life	Variation of perceived quality of life with a single overall item from PQOL scale	From inclusion to Day 7 (or hospital discharge if it happens first) and Day 90.
Secondary	Variation of IADL test	Variation of IADL test	From inclusion to Day 90.
Secondary	Death rate from all causes	Death rate from all causes	From inclusion to Day 90
Secondary	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	From inclusion to Day 90