Efficacy of Ferric Carboxymaltose With or Without EPO Reducing Red-cell Transfusion Packs in Hip Fracture Perioperative Period

Study Overview
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Brief Summary
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In order to evaluate the efficacy of ferric carboxymaltose + erythropoietin versus ferric carboxymaltose versus placebo in reducing the percentage of patients who receive red-cell transfusion in the perioperative period of hip fracture, a multicenter, randomized, parallel groups, double-blind clinical trial in adult patients admitted for osteoporotic hip fracture is designed. Required sample size is of 87 patients per arm (87x3 = 261). Primary efficacy variable is the percentage of patients who receive red-cell transfusion during hospitalization; secondary end-points: average red-cell packs per patient,haemoglobin at 24 h and 72h after the intervention, at the time of hospital discharge and 60 days after hospital discharge, hospital stay and mortality during hospital-stay and 60 days afterwards. Adverse clinical events and side effects are assessed as safety variables. In addition health related quality of life will be measured at inclusion and after 60 days. A cost-efficacy analysis (by means of incremental cost-efficacy method using as a primary endpoint each patient not requiring transfusion, and as secondary end-point every patient who survived the index admission is performed). The investigators would like to demonstrate a double benefits: optimizing precious resource such as blood products and reducing complications arising from their use.

Detailed Description
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Three arms of treatments: A: ferric carboxymaltose and erythropoietin, B: ferric carboxymaltose and placebo, arm C: two placebos. Primary objective:reduction of red-cell packs needed for elderly patients with osteoporotic hip fracture which requires surgical intervention in the perioperative period.

Official Title
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Multicenter Double-bind Randomized Trial of Ferric Carboxymaltose With or Without Erythropoietin for the Prevention of Red-cell Transfusion in Hip Fracture Perioperative Period.

Conditions
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Hip Fractures

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Erythropoietin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 65 years and older. Osteoporotic hip fracture which require surgical intervention Haemoglobin levels between 90-120 g/L Signed informed consent form Exclusion Criteria: Bone marrow diseases which could interfere in the erythropoietic process (acute or chronic myelodysplastic syndromes or myeloproliferative diseases, and/or infiltration of the bone marrow due to solid or lymphatic neoplasms) Blood coagulation diseases or currently treated with oral anticoagulants and/or heparin at therapeutic doses. Documented allergy and/or previous intolerance and/or contraindication of erythropoietin use and/or intravenous iron. Patients with rheumatoid arthritis and/or another demonstrated origin of inflammatory anemia and/or not controlled arterial hypertension.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two placebos: placebo for ferric carboxymaltose and placebo for erythropoietin | Drug: Placebo<br>* Placebo for ferric carboxymaltose: 250 mL normal saline for intravenous administration. Placebo for erythropoietin: 1 mL normal saline for subcutaneous injection.<br>|
| Experimental: FE<br>Ferric carboxymaltose and placebo for erythropoietin | Drug: Ferric carboxymaltose<br>* Ferinject®: Ferric carboxymaltose: 2 vials of 10 mL containing each 500 mg iron, diluted in 250 mL normal saline for injection. Study drug to be administered by infusion immediately after preparation. Placebo for erythropoietin: 1 mL normal saline for subcutaneous injection.<br>* Other names: Intravenous iron;|
| Experimental: EPOFE<br>Ferric carboxymaltose and erythropoietin | Drug: Ferric carboxymaltose<br>* Ferinject®: Ferric carboxymaltose: 2 vials of 10 mL containing each 500 mg iron, diluted in 250 mL normal saline for injection. Study drug to be administered by infusion immediately after preparation. Placebo for erythropoietin: 1 mL normal saline for subcutaneous injection.<br>* Other names: Intravenous iron;Drug: Erythropoietin<br>* Erythropoetin: 40,000 units subcutaneous (unique dose).<br>* Other names: EPO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduce red-cell transfusion packs | percentage of patients who receive red-cell transfusion during hospitalization | 60 days after hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average red-cell packs per patient |  | end of study | 
| Haemoglobin level |  | 24 h and 72h after the intervention, at the time of hospital discharge and 60 days after hospital discharge | 
| Number of hospitalization days | number of days inhospital | end of study | 
| Death rate with all causes mortality |  | end of study | 
| Adverse Events | adverse clinical events, side effects, Serious Adverse Events (SAE) and Suspected Unexpected Serious Adverse Reaction(SUSAR) | end of study | 
| Quality of life | health related quality of life | end of study | 
| cost-efficacy analysis | means of incremental cost-efficacy method (using as a primary endpoint each patient not requiring transfusion, and as secondary end-point every patient who survived the index admission) | end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hip fractures, blood substitutes, blood transfusion, intravenous infusion, erythropoietin, recombinant, frail elderly