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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02972294
Recruitment Status : Terminated (1year inclusion hold due to PV new fact (Monofer hold for risk revaluation) DSMB Interim analysis : 1treatment with important transfusion risk reduction/inclusions issues (COVID)/sites change of practice if study continue=>stop inclusions)
First Posted : November 23, 2016
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Angers

Tracking Information
First Submitted Date  ICMJE November 21, 2016
First Posted Date  ICMJE November 23, 2016
Last Update Posted Date August 2, 2022
Actual Study Start Date  ICMJE March 31, 2017
Actual Primary Completion Date September 16, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2016)
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 D30 if patient is still hospitalized). ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2020)
  • 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)
  • 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
  • Hemoglobin concentration [ Time Frame: At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30. ]
    Hemoglobin concentration
  • 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)
  • Reticulocytes count [ Time Frame: On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery ]
    Reticulocytes count
  • 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)
  • 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
  • Number of hospitalization days [ Time Frame: On Day 30 and Day 90 following surgery. ]
    Number of hospitalization days
  • 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)
  • 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
  • Variation of quality of life [ Time Frame: From inclusion to Day 30 and Day 90 ]
    Variation of EQ-5D score
  • 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
  • Variation of IADL test [ Time Frame: From inclusion to Day 90. ]
    Variation of IADL test
  • Death rate from all causes [ Time Frame: 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 [ 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2016)
  • Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units [ Time Frame: During first week posteratively, hospital stay and till one month following surgery. ]
  • Hemoglobin concentration [ Time Frame: On days 3, 7 (or hospital discharge if it happens first) and 30. ]
  • Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men) [ Time Frame: On days 3, 7 (or hospital discharge if it happens first) and 30. ]
  • Reticulocytes count [ Time Frame: On days 7 (or hospital discharge if it happens first) and 30 ]
  • Perioperative blood loss (estimated according to a formula based on hematocrit variation). [ Time Frame: During surgery ]
  • Iron deficiency (defined as a ferritin < 100 ng/ml or < 300 ng/ml together with transferrin saturation <20%), ferritin and transferrin saturation [ Time Frame: On D7 (or hospital discharge if it happens first) and D30. ]
  • Number of hospitalization days [ Time Frame: On D30 and D90 following surgery. ]
  • Proportion of patients at home [ Time Frame: On D30 and D90. ]
  • Proportion of patients able to walk a distance of ten feet without assistance [ Time Frame: On D30 and D90 ]
  • Variation of EQ-5D score from inclusion to D30 and D90 [ Time Frame: From inclusion to D30 and D90 ]
  • Variation of perceived quality of life with a single overall item from PQOL scale [ Time Frame: From inclusion to D7 (or hospital discharge if it happens first) and D90. ]
  • Variation of IADL test [ Time Frame: From inclusion to D90. ]
  • Death rate from all causes [ Time Frame: From inclusion to D90 ]
  • Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications [ Time Frame: In the month following surgery ]
Current Other Pre-specified Outcome Measures
 (submitted: November 15, 2020)
  • 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
  • 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)
  • 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,
Original Other Pre-specified Outcome Measures
 (submitted: November 21, 2016)
  • Maximum strength of the hand and forearm muscles 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 [ 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. [ Time Frame: On day 7 (or hospital discharge if it happens first) ]
 
Descriptive Information
Brief Title  ICMJE HiFIT Study : Hip Fracture: Iron and Tranexamic Acid
Official Title  ICMJE HiFIT Study: Interest of Intravenous Iron and Tranexamic Acid to Reduce Transfusion in Hip Fracture Patients
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Hip Fractures Pathologic
  • Anemia
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: TXA + IIM
    The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid
    Interventions:
    • Drug: Iron Isomaltoside 1000
    • Drug: Tranexamic Acid
  • Experimental: Placebo TXA + IIM
    The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid
    Interventions:
    • Drug: Iron Isomaltoside 1000
    • Drug: Placebos tranexamic acid
  • Experimental: TXA + Placebo IIM
    The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid
    Interventions:
    • Drug: Tranexamic Acid
    • Drug: Placebos iron isomaltoside 1000
  • Experimental: Placebo TXA + Placebo IIM
    The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid
    Interventions:
    • Drug: Placebos iron isomaltoside 1000
    • Drug: Placebos tranexamic acid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 9, 2021)
419
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2016)
780
Actual Study Completion Date  ICMJE September 16, 2021
Actual Primary Completion Date September 16, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02972294
Other Study ID Numbers  ICMJE 49RC16_0014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University Hospital, Angers
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Angers
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sigismond SL Lasocki, PU-PH UNIVERSITE HOSPITAL, ANGERS
PRS Account University Hospital, Angers
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP