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HiFIT Study : Hip Fracture: Iron and Tranexamic Acid (HiFIT)

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ClinicalTrials.gov Identifier: NCT02972294
Recruitment Status : Recruiting
First Posted : November 23, 2016
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hip Fractures Pathologic Anemia Drug: Iron Isomaltoside 1000 Drug: Tranexamic Acid Drug: Placebos iron isomaltoside 1000 Drug: Placebos tranexamic acid Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 780 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: HiFIT Study: Interest of Intravenous Iron and Tranexamic Acid to Reduce Transfusion in Hip Fracture Patients
Actual Study Start Date : March 31, 2017
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: TXA + IIM
The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid
Drug: Iron Isomaltoside 1000
Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment
Other Name: monofer

Drug: Tranexamic Acid
Tranexamic acid will be use.
Other Name: exacyl

Experimental: Placebo TXA + IIM
The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid
Drug: Iron Isomaltoside 1000
Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment
Other Name: monofer

Drug: Placebos tranexamic acid
placebo of tranexamic acid correspond to a saline solution.
Other Name: saline serum

Experimental: TXA + Placebo IIM
The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid
Drug: Tranexamic Acid
Tranexamic acid will be use.
Other Name: exacyl

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
Other Name: saline serum

Experimental: Placebo TXA + Placebo IIM
The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid
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
Other Name: saline serum

Drug: Placebos tranexamic acid
placebo of tranexamic acid correspond to a saline solution.
Other Name: saline serum




Primary Outcome Measures :
  1. Proportion of patients who received a blood transfusion during their hospital stay following surgery [ Time Frame: 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 :
  1. Proportion of patients who received a blood transfusion after surgery [ Time Frame: 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)

  2. Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units [ Time Frame: 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

  3. Hemoglobin concentration [ Time Frame: At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30. ]
    Hemoglobin concentration

  4. Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men) [ Time Frame: 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)

  5. Reticulocytes count [ Time Frame: On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery ]
    Reticulocytes count

  6. Perioperative blood loss (estimated according to a formula based on hematocrit variation). [ Time Frame: 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)

  7. Post operative Iron deficiency rate [ Time Frame: 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

  8. Number of hospitalization days [ Time Frame: On Day 30 and Day 90 following surgery. ]
    Number of hospitalization days

  9. Proportion of patients at home [ Time Frame: On Day 30 and Day 90. ]
    Proportion of patients returned at home (or at their previous place of living)

  10. Proportion of patients able to walk a distance of ten feet without assistance [ Time Frame: On Day 30 and Day 90 ]
    Proportion of patients able to walk a distance of ten feet without assistance

  11. Variation of quality of life [ Time Frame: From inclusion to Day 30 and Day 90 ]
    Variation of EQ-5D score

  12. Variation of perceived quality of life [ Time Frame: 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

  13. Variation of IADL test [ Time Frame: From inclusion to Day 90. ]
    Variation of IADL test

  14. Death rate from all causes [ Time Frame: From inclusion to Day 90 ]
    Death rate from all causes

  15. Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications [ Time Frame: 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


Other Outcome Measures:
  1. Strength assessed by the Hand Grip Strength test [ Time Frame: On day 7 (or hospital discharge if it happens first) ]
    Maximum strength of the hand and forearm muscles assessed by the Hand Grip Strength test

  2. Muscular fatigability assessed by the Hand Grip Strength test [ Time Frame: On day 7 (or hospital discharge if it happens first) ]
    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)

  3. Level of locomotion and balance assessed by the Timed " Up and Go " test. [ Time Frame: On day 7 (or hospital discharge if it happens first) ]
    Level of locomotion and balance assessed by the Timed " Up and Go " test,



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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02972294


Contacts
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Contact: Sigismond SL Lasocki, PU-PH 02 41 35 36 35 ext 33 SiLasocki@chu-angers.fr

Locations
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France
CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION Recruiting
Angers, France, 49000
Contact: SIGISMOND SL LASOCKI, PUPH         
Sub-Investigator: EMMANUEL ER RINEAU, CCA         
Principal Investigator: SIGISMOND SL LASOCKI, PUPH         
Sub-Investigator: MATHIEU MC CONTE, PH         
Sub-Investigator: GUILLAUME GB BOUHOURS, PH         
Sub-Investigator: EMMANUEL ES SAMSON, CCA         
Clinique de L'Anjou- Anesthesie Reanimation Active, not recruiting
Angers, France, 49000
HIA Clermont-Tonnerre Recruiting
Brest, France
Contact: Marc Danguy des Déserts, MD         
Contact       marc.danguydesdeserts@intradef.gouv.fr   
Chu Grenoble - Departement D'Anesthesie Reanimation Recruiting
Grenoble, France, 38043
Contact: PIERRE PA Bouzat, PUPH         
Principal Investigator: PIERRE PB Bouzat, PUPH         
Sub-Investigator: GAETAN GG GAZAZI         
CHD Vendée Recruiting
La Roche-sur-Yon, France
Contact: Alexis Duchalais, MD         
Contact       alexis.duchalais@chd-vendee.fr   
Ramsay Santé, Clinique de la Sauvegarde Recruiting
Lyon, France
Contact: Olivier Desebbe, MD         
Chu Montpellier - Departement D'Anesthesie Reanimation Recruiting
Montpellier, France, 34295
Contact: XAVIER XC CAPDEVILA, PUPH         
Principal Investigator: XAVIER XC CAPDEVILA, PUPH         
Sub-Investigator: THIBAULT TL LOUPEC, MD         
Sub-Investigator: OLIVIER OC CHOQUET, MD         
Sub-Investigator: Benjamin Mounet, MD         
Chu Nantes- Service de Reanimation Chirurgicale Recruiting
Nantes, France, 44093
Contact: KARIM KA ASEHNOUNE, PUPH         
Principal Investigator: KARIM KA ASEHNOUNE, PUPH         
Sub-Investigator: AURORE AD DESDOITS, MD         
Principal Investigator: Antoine Roquilly, PUPH         
Chu Poitiers - Service D'Anesthesie Reanimation Recruiting
Poitiers, France, 86000
Contact: BERTRAND BD DRUGEON, MD         
Sub-Investigator: BERTRAND BD DEBAENE, PUPH         
Sub-Investigator: FRANCK FC CHEVALIER         
Sub-Investigator: JEAN MATTHIEU JB BRASSEUR         
Sub-Investigator: LOUIS MARIE LA AUTET         
Principal Investigator: Bertrand Drugeon, MD         
Chu Rennes - Service D'Anesthesie Reanimation Recruiting
Rennes, France, 35033
Contact: HELENE HB BELOEIL, PH         
Principal Investigator: HELENE HB BELOEIL, PH         
Principal Investigator: MARIA ML LAHLOU, CCA         
Medipôle Recruiting
Villeurbanne, France
Contact: Vincent Collange, MD         
Contact       collangev@gmail.com   
Sponsors and Collaborators
University Hospital, Angers
Investigators
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Study Director: Sigismond SL Lasocki, PU-PH UNIVERSITE HOSPITAL, ANGERS
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT02972294    
Other Study ID Numbers: 49RC16_0014
First Posted: November 23, 2016    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Angers:
iron isomaltoside
tranexamic acid
Additional relevant MeSH terms:
Layout table for MeSH terms
Fractures, Bone
Hip Fractures
Wounds and Injuries
Femoral Fractures
Hip Injuries
Leg Injuries
Iron
Tranexamic Acid
Iron isomaltoside 1000
Ferric Compounds
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematinics