HiFIT Study : Hip Fracture: Iron and Tranexamic Acid

Phase 3

Terminated

• Conditions: Hip Fractures Pathologic; Anemia
• Interventions: Drug: Iron Isomaltoside 1000; Drug: Placebos tranexamic acid; Drug: Placebos iron isomaltoside 1000; Drug: Tranexamic Acid

• Registration Number: NCT02972294
• Lead Sponsor: University Hospital, Angers

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.

Study Timeline

• Study First Submitted: 2016-11-21
• Study First Submitted QC: 2016-11-21
• Study First Posted: 2016-11-23
• Study Start: 2017-03-31
• Primary Completion: 2021-09-16
• Study Completion: 2021-09-16
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-28
• Last Update Posted: 2022-08-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 419

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
TXA + IIM	Iron Isomaltoside 1000	The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid
Placebo TXA + IIM	Placebos tranexamic acid	The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid
TXA + Placebo IIM	Placebos iron isomaltoside 1000	The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid
Placebo TXA + Placebo IIM	Placebos tranexamic acid	The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid
Placebo TXA + Placebo IIM	Placebos iron isomaltoside 1000	The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid
TXA + IIM	Tranexamic Acid	The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid
Placebo TXA + IIM	Iron Isomaltoside 1000	The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid
TXA + Placebo IIM	Tranexamic Acid	The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid

Primary Outcome Measures

Name	Time	Method
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).	Proportion of patients who received a blood transfusion during their hospital stay following surgery

Secondary Outcome Measures

Name	Time	Method
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)	Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units
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.	Proportion of patients with anemia (hemoglobin \<12 g/dL in women and \<13 g/dL in men)
Proportion of patients able to walk a distance of ten feet without assistance	On Day 30 and Day 90	Proportion of patients able to walk a distance of ten feet without assistance
Variation of quality of life	From inclusion to Day 30 and Day 90	Variation of EQ-5D score
Variation of perceived quality of life	From inclusion to Day 7 (or hospital discharge if it happens first) and Day 90.	Variation of perceived quality of life with a single overall item from PQOL scale
Variation of IADL test	From inclusion to Day 90.	Variation of IADL test
Death rate from all causes	From inclusion to Day 90	Death rate from all causes
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	Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications
Perioperative blood loss (estimated according to a formula based on hematocrit variation).	During surgery	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)
Post operative Iron deficiency rate	On Day 7 (or hospital discharge if it happens first) and Day 30.	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
Number of hospitalization days	On Day 30 and Day 90 following surgery.	Number of hospitalization days
Proportion of patients at home	On Day 30 and Day 90.	Proportion of patients returned at home (or at their previous place of living)
Proportion of patients who received a blood transfusion after surgery	From the day of surgery until Day 3, Day 7 and Day 30 post surgery.	Proportion of patients who received a blood transfusion during the month following surgery (including fresh frozen plasma and platelets)
Hemoglobin concentration	At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30.	Hemoglobin concentration
Reticulocytes count	On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery	Reticulocytes count

Trial Locations

Locations (13)

Chu Grenoble - Departement D'Anesthesie Reanimation; 🇫🇷 Grenoble, France

CHD Vendée; 🇫🇷 La Roche-sur-Yon, France

Hospices Civils Lyon; 🇫🇷 Lyon, France

Clinique de L'Anjou- Anesthesie Reanimation; 🇫🇷 Angers, France

CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION; 🇫🇷 Angers, France

HIA Clermont-Tonnerre; 🇫🇷 Brest, France

CHU Lille; 🇫🇷 Lille, France

Ramsay Santé, Clinique de la Sauvegarde; 🇫🇷 Lyon, France

Chu Poitiers - Service D'Anesthesie Reanimation; 🇫🇷 Poitiers, France

Chu Montpellier - Departement D'Anesthesie Reanimation; 🇫🇷 Montpellier, France

Chu Nantes- Service de Reanimation Chirurgicale; 🇫🇷 Nantes, France

Chu Rennes - Service D'Anesthesie Reanimation; 🇫🇷 Rennes, France

Medipôle; 🇫🇷 Villeurbanne, France