HiFIT Study : Hip Fracture: Iron and Tranexamic Acid

NCT ID: NCT02972294

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 419 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-31
• Study Completion Date: 2021-09-16

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.

Conditions

Hip Fractures Pathologic; Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TXA + IIM

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

Group Type: EXPERIMENTAL

Iron Isomaltoside 1000

Intervention Type: DRUG

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

Tranexamic Acid

Intervention Type: DRUG

Tranexamic acid will be use.

Placebo TXA + IIM

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

Group Type: EXPERIMENTAL

Iron Isomaltoside 1000

Intervention Type: DRUG

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

Placebos tranexamic acid

Intervention Type: DRUG

placebo of tranexamic acid correspond to a saline solution.

TXA + Placebo IIM

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

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

Tranexamic acid will be use.

Placebos iron isomaltoside 1000

Intervention Type: DRUG

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

Placebo TXA + Placebo IIM

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

Group Type: EXPERIMENTAL

Placebos iron isomaltoside 1000

Intervention Type: DRUG

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

Intervention Type: DRUG

placebo of tranexamic acid correspond to a saline solution.

Interventions

Iron Isomaltoside 1000

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

Intervention Type: DRUG

Tranexamic Acid

Tranexamic acid will be use.

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebos tranexamic acid

placebo of tranexamic acid correspond to a saline solution.

Intervention Type: DRUG

Other Intervention Names

monofer; exacyl; saline serum; saline serum

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sigismond SL Lasocki, PU-PH

Role: STUDY_DIRECTOR

UNIVERSITE HOSPITAL, ANGERS

Locations

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, , France

Countries

France

References

Lasocki S, Capdevila X, Bijok B, Lahlou-Casulli M, Collange V, Grillot N, Loupec T, Rineau E, Leger M; HiFIT Investigators. Quality of life of patients with hip fracture was better during the COVID-19 period than before, an ancillary study from the HiFIT multicenter study. Front Public Health. 2024 Apr 16;12:1362240. doi: 10.3389/fpubh.2024.1362240. eCollection 2024.

Reference Type: DERIVED

PMID: 38689774 (View on PubMed)

Lasocki S, Capdevila X, Vielle B, Bijok B, Lahlou-Casulli M, Collange V, Grillot N, Danguy des Deserts M, Duchalais A, Delannoy B, Drugeon B, Bouzat P, David JS, Rony L, Loupec T, Leger M, Rineau E; HiFIT Investigators; SFAR research network. Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 x 2 factorial, randomised, double-blind, controlled trial. Lancet Haematol. 2023 Sep;10(9):e747-e755. doi: 10.1016/S2352-3026(23)00163-1. Epub 2023 Jul 28.

Reference Type: DERIVED

PMID: 37524101 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33781988 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33455926 (View on PubMed)

Other Identifiers

49RC16_0014

Identifier Type: -

Identifier Source: org_study_id