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

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

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.

Study Overview

• Status: Completed
• Conditions: Hip Fractures
• Intervention / Treatment: Drug: Placebo; Drug: Ferric carboxymaltose; Drug: Erythropoietin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Albacete, Spain, 02006
    • Hospital Universitario de Albacete
  • Huelva, Spain, 21080
    • Hospital Infanta Elena
  • Lugo, Spain, 27004
    • Hospital Lucus Augusti
  • Seville, Spain
    • Hospital Universitario Virgen Macarena
  • Valladolid, Spain
    • Hospital Universitario Rio Hortega
  • Alicante
    • Elche, Alicante, Spain
      • Hospital General Universitario de Elche
    • Orihuela, Alicante, Spain, 03314
      • Hospital de La Vega Baja
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
      • Hospital Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • España
    • Sevilla, España, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Guipúzcoa
    • San Sebastián, Guipúzcoa, Spain
      • Hospital Donostia
  • Malaga
    • Ronda, Malaga, Spain, 29400
      • Hospital de la Serranía de Ronda
  • Málaga
    • Vélez-Málaga, Málaga, Spain
      • Hospital Comarcal de la Axarquia
  • Sevilla
    • Bormujos, Sevilla, Spain, 41930
      • Hospital San Juan de Dios del Aljarafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Two placebos: placebo for ferric carboxymaltose and placebo for erythropoietin	Drug: Placebo; Placebo for ferric carboxymaltose: 250 mL normal saline for intravenous administration. Placebo for erythropoietin: 1 mL normal saline for subcutaneous injection.
Experimental: FE; Ferric carboxymaltose and placebo for erythropoietin	Drug: Ferric carboxymaltose; 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.; Other Names: Intravenous iron
Experimental: EPOFE; Ferric carboxymaltose and erythropoietin	Drug: Ferric carboxymaltose; 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.; Other Names: Intravenous iron; Drug: Erythropoietin; Erythropoetin: 40,000 units subcutaneous (unique dose).; Other Names: EPO

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: Máximo Bernabeu-Wittel, MD, Hospital Universitario Virgen del Rocio. Sevilla

Publications and helpful links

General Publications

• Bernabeu-Wittel M, Romero M, Ollero-Baturone M, Aparicio R, Murcia-Zaragoza J, Rincon-Gomez M, Monte-Secades R, Melero-Bascones M, Rosso CM, Ruiz-Cantero A; PAHFRAC-01 Investigators. Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial. Transfusion. 2016 Sep;56(9):2199-211. doi: 10.1111/trf.13624. Epub 2016 May 14.
• Bernabeu-Wittel M, Aparicio R, Romero M, Murcia-Zaragoza J, Monte-Secades R, Rosso C, Montero A, Ruiz-Cantero A, Melero-Bascones M; PAHFRAC-01 investigators. Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project. BMC Musculoskelet Disord. 2012 Feb 21;13:27. doi: 10.1186/1471-2474-13-27.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: June 24, 2010
• First Submitted That Met QC Criteria: June 30, 2010
• First Posted (Estimate): July 1, 2010

Study Record Updates

• Last Update Posted (Estimate): July 28, 2015
• Last Update Submitted That Met QC Criteria: July 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: frail elderly; blood transfusion; hip fractures; blood substitutes; intravenous infusion; erythropoietin, recombinant
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Hematinics; Epoetin Alfa
• Other Study ID Numbers: PAHFRAC-01; 2009-015865-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No