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 Musculoskeletal Disorders

María Melero-Bascones⁴  Alberto Ruiz-Cantero⁶  Abelardo Montero⁹  Clara Rosso⁵  Rafael Monte-Secades³  José Murcia-Zaragoza²  Manuel Romero⁸  Reyes Aparicio⁷  Máximo Bernabeu-Wittel¹ 

[1] Department of Internal Medicine, Hospitales Universitarios Virgen del Rocío, Avenida Manuel Siurot s/n., 41013 Sevilla, Spain;Hospital de la Vega Baja, Orihuela, Alicante, Spain;Complexo Hospitalario Xeral-Calde, Lugo, Spain;Hospital General Universitario de Albacete, Albacete, Spain;Hospital Universitario Virgen del Rocío, Sevilla, Spain;Hospital de la Serranía, Ronda, Málaga, Spain;Hospital San Juan de Dios del Aljarafe, Sevilla, Spain;Hospital Infanta Elena, Huelva, Spain;Hospital Universitario de Bellvitge, Barcelona, Spain

关键词: Clinical trial;    Red-cell pack;    Erythropoietin;    Ferric carboxymaltose;    Blood-saving strategies;    Transfusion;    Hip fracture;   

Others  :  1150423
DOI  :  10.1186/1471-2474-13-27

 received in 2011-11-12, accepted in 2012-02-21,  发布年份 2012

【 摘 要 】

Background

Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention.

Methods/Design

Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients.

Discussion

We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491.

【 授权许可】

   
2012 Bernabeu-Wittel et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Alvarez-Nebreda ML, Jiménez AB, Rodríguez P, Serra JA: Epidemiology of hip fracture in the elderly in Spain. Bone 2008, 42:278-285.
• [2]Cummings SR, Rubin SM, Black D: The future of hip fractures in the United States: numbers, costs, and potential effects of postmenopausal estrogen. Clin Orthop 1990, 252:163-166.
• [3]Kannus P, Parkkari J, Sievännen H, Heinonen A, Vuori I, Järvinen M: Epidemiology of hip fractures. Bone 1996, 18(suppl 1):57S-63S.
• [4]Ceder L, Thorngren KG, Wallden B: Prognostic indicators and early home rehabilitation in elderly patients with hip fractures. Clin Orthop 1980, 152:173-184.
• [5]Jette AM, Harris BA, Cleary PD, et al.: Functional recovery after hip fracture. Arch Phys Med Rehabil 1987, 68:735-740.
• [6]Las fracturas de cadera suponen un coste de 25000 millones de euros al año en la UE ReES 2005, 4:216-217.
• [7]Carlson JL, Terrin ML, Barton FB, et al.: A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red blood cell transfusions following hip fracture. Transfusion 1998, 38:522-529.
• [8]Van Iperen CE, Kraaijenhagen RJ, Biesma DH, et al.: Iron metabolism and erythropoiesis after surgery. Br J Surg 1998, 85:41-45.
• [9]Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP: Transfusion medicine. N Engl J Med 1999, 340:438-447.
• [10]Hill GE, Frawley WH, Griffith KE, Forestner JE, Minei JP: Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis. J Trauma 2003, 54:908-914.
• [11]Carson JL, Duff A, Berlin JA, et al.: Perioperative blood transfusion and postoperative mortality. JAMA 1998, 279:199-205.
• [12]Izuel Rami M, Gómez Barrera M, Villar Fernández I, et al.: Análisis del impacto presupuestario de la implantación de medidas de ahorro de sangre en cirugía de urgencia. Medicina Clínica (Barc.) 2007, 128(1):7-11.
• [13]Naglie G, Tansey C, Kirkland JL, et al.: Interdisciplinary inpatient care for elderly people with hip fracture: a randomized controlled trial. CMAJ 2002, 167:25-32.
• [14]Izuel-Rami M, Cuenca Espiérrez J, García-Erce JA, et al.: Efectividad de las distintas pautas de tratamiento de la anaemia perioperatoria en pacientes ancianos con fractura de cadera. Farm Hosp 2005, 29:250-257.
• [15]Karnouki K, McCluskey SA, Grahnnam M, et al.: Intravenous iron and recombinant erythropoietin for the treatment of postoperative anaemia. Can J Anesth 2006, 53:11-19.
• [16]Cuenca J, García-Erce JA, Muñoz M, et al.: Patients with pertrochanteric hip fracture may benefit from preoperative intravenous iron therapy: a pilot study. Transfusion 2004, 44:1447-1452.
• [17]Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, et al.: A novel intravenous iron formulation for treatment of anaemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol 2008, 103:1182-1192.
• [18]Breymann C, Gliga F, Bejenariu C, Strizhova N: Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anaemia. Int J Gynaecol Obstet 2008, 101:67-73.
• [19]Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A: Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anaemia: a randomized controlled trial. Obstet Gynecol 2007, 110:267-278.
• [20]Alonso J, Prieto L, Anto JM: La versión española del SF-36 Health Survey (Cuestionario de Salud SF-36): un instrumento para la medida de los resultados clínicos. Med Clin (Barc) 1995, 104:771-776.
• [21]Cuenca J, García-Erce A, Martínez AA, et al.: Role of parenteral iron in the management of anaemia in the elderly patient undergoing displaced subcapital hip fracture repair: preliminary data. Arch Orthop Trauma Surg 2005, 125:342-347.
• [22]Keating EM, Meding JB: Perioperative blood management practices in elective orthopaedic surgery. J Am Acad Orthop Surg 2002, 10:393-400.
• [23]Goldberg MA: Perioperative epoetin alfa increases red blood cell mass and reduces exposure to transfusions: results of randomized clinical trials. Semin Hematol 1997, 34:41-47.
• [24]Faris PM, Ritter MA, Abels RI: The effects of recombinant human erythropoietin on perioperative transfusion requirements in patients having a major orthopaedic operation. The American Erythropoietin Study Group. J Bone Joint Surg Am 1996, 78:62-72.
• [25]Goldberg MA, McCutchen JW, Jove M, Di Cesare P, Friedman RJ, Poss R, Guilfoyle M, Frei D, Young D: A safety and efficacy comparison study of two dosing regimens of epoetin alfa in patients undergoing major orthopedic surgery. Am J Orthop 1996, 25:544-552.
• [26]Lofthouse RA, Boitano MA, Davis JR, Jinnah RH: Preoperative administration of epoetin alfa to reduce transfusion requirements in elderly patients having primary total hip or knee reconstruction. J South Orthop Assoc 2000, 9:175-181.
• [27]Rauh MA, Bayers-Thering M, LaButti RS, Krackow KA: Preoperative administration of epoetin alfa to total joint arthroplasty patients. Orthopedics 2002, 25:317-320.
• [28]de Andrade JR, Jove M, Landon G, Frei D, Guilfoyle M, Young DC: Baseline hemoglobin as a predictor of risk of transfusion and response to epoetin alfa in orthopedic surgery patients. Am J Orthop 1996, 25:533-542.
• [29]Auerbach M, Coyne D, Ballard H: Intravenous iron: from anathema to standard of care. Am J Hematol 2008, 83:580-588.
• [30]MacDougall IC: Intravenous administration of iron in epoetin-treated haemodialysis atients--which drugs, which regimen? Nephrol Dial Transplant 2000, 15:1743-1745.
• [31]Goodnough LT, Shander A, Spence R: Bloodless medicine: clinical care without allogeneic blood transfusion. Transfusion 2003, 43:668-676.
• [32]Silverstein SB, Rodgers GM: Parenteral iron therapy options. Am J Hematol 2004, 76:74-78.
• [33]Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P: FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009, 361:2436-2448.
• [34]Bisbe E, García-Erce JA, Díez-Lobo AI, Muñoz M: A multicentre comparative study on the efficacy of intravenous ferric carboxymaltose and iron sucrose for correcting preoperative anaemia in patients undergoing major elective surgery. Br J Anaesth 2011, 107:477-478.