Comparing Intravenous and Oral Iron in Postoperative Anemia

Efficacy of Intravenous Ferric Carboxymaltose in the Improvement of Anemia in Patients With Postoperative Knee Prosthesis

Postoperative anaemia are common in patients undergoing major orthopaedic surgery. The main consequence of perioperative anaemia is an increased risk of red blood cell (RBC) transfusions. Allogeneic RBC transfusion and anaemia are associated with higher postoperative mortality and morbidity.

The aim of this study was to compare the efficacy of postoperative i.v. ferric carboxymaltose (FCM) and oral ferrous glycine sulphate (FS) for early improvement of postoperative anaemia after total knee arthroplasty and whether iron treatment could facilitate recovery from surgery.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee; Postoperative Anemia
• Intervention / Treatment: Drug: Ferric carboxymaltose; Drug: ferrous glycine sulphate

Detailed Description

Both pre- and postoperative anaemia are common in patients undergoing major orthopaedic surgery. The main consequence of perioperative anaemia is an increased risk of red blood cell (RBC) transfusions. Allogeneic RBC transfusion and anaemia are associated with higher postoperative mortality and morbidity. Since blood transfusions increase Hb levels only transiently but come at the price of higher mortality and morbidity (e.g. postoperative infections), the three-pillar concept of patient blood management (PBM) has been developed to reduce the risk of blood transfusions and improve patient outcomes. Among its three pillars, the treatment or prevention of preoperative anaemia is the mainstay of PBM. Also the second pillar, minimisation of intraoperative blood loss,15 targets at least indirectly the patient's haemoglobin (Hb) levels.

The third PBM pillar, use of low Hb cut-off levels triggering transfusion, means that a certain degree of postoperative anaemia is taken into account. However, it remains unclear whether a lowered transfusion threshold allows optimal functional recovery and quality of life. Since patients undergoing total knee arthroplasty (TKA) are often elderly and have several comorbidities, prolonged exposure to low Hb levels is not a good option for this population. Furthermore, TKA patients should be mobilised as soon as possible after surgery which increases the metabolic demand.

Although, depending on the timescale before surgery, oral iron is suggested for preoperatively anaemic patients with absolute iron deficiency, oral iron showed no benefit over placebo in anaemic patients after lower limb arthroplasty. In patients at risk of functional iron deficiency due to chronic inflammation of different aetiologies, intravenous (i.v.) iron administration has proven its superiority over oral iron. Even in iron-deficient patients without established anaemia, i.v. iron improved physical performance and cardiac functional class. Thus, postoperative anaemia treatment with i.v. iron might not only reduce RBC requirements but also improve performance, rehabilitation and outcomes.

The aim of this study was to compare the efficacy of postoperative i.v. ferric carboxymaltose (FCM) and oral ferrous glycine sulphate (FS) for early improvement of postoperative anaemia after total knee arthroplasty and whether iron treatment could facilitate recovery from surgery.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08024
    • Hospital de la Esperanza (Parc de Salut MAR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (≥18 years of age) were recruited at the scheduled preoperative visit (21 to 30 days prior surgery knee replacement). Anaemia (Hb <12 g/dL) and/or iron deficiency (TSAT <20%) the day after surgery

Exclusion Criteria:

• Patients with known hypersensitivity or contraindications to iron, liver insufficiency (aspartate aminotransferase or alanine aminotransferase >60 IU/L), bronchial asthma, presence of acute or chronic infection, severe heart disease, significant history of allergies (rash, etc.) or anti-anaemia treatment within 15 days prior to surgery were excluded from participation. Also pregnant or nursing women were excluded (negative pregnancy urine test within 7 days prior first study treatment or amenorrhoea for at least 12 months).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferric carboxymaltose; Ferric carboxymaltose (Ferinject®, Vifor-France) was given as a single i.v. dose to correct the total iron deficit calculated by the Ganzoni formula (total iron deficit [mg] = 2.4 x patient's weight [kg] x (target Hb [13 g/dL] - current Hb [g/dL]) + 500 [mg iron stores]	Drug: Ferric carboxymaltose; Single intravenous dose ferric carboxymaltose; Other Names: intravenous iron
Active Comparator: Ferrous glycine sulphate; Ferrous glycine sulphate (Ferbisol-Bial Industrial Farmacéutica, Spain) was given as a once daily oral dose of 100 mg iron from the day of discharge (Day 7) to the rehabilitation visit 30 days after surgery	Drug: ferrous glycine sulphate; Daily oral dose of 100 mg iron (ferrous glycine sulphate); Other Names: Oral iron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin concentration	Change in hemoglobin concentrations from baseline to 30 days	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia	Number of subjects without anemia (hemoglobin > 12g/dL)	30 days
Hemoglobin concentration	Concentration of hemoglobin at day 30	30 days
Quality of life	Quality of life measured by European Quality of Life-5 Dimensions (EQ-5D)(before and 30 days)	30 days
Independence in daily activities	Independence in daily activities measured by the Barthel questionnaire (before and 30 days)	30 days
Walk test	6 minutes walking test (before and 30 days)	30 days
Adverse events	Adverse event (clinical and analytical, before to 30 days)	30 days

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Vifor Pharma
• Investigators: Study Director: Elvira Bisbe, MD, Parc de Salut Mar; Principal Investigator: Luis Molto, MD, Parc de Salut Mar

Publications and helpful links

General Publications

• Bisbe E, Molto L, Arroyo R, Muniesa JM, Tejero M. Randomized trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty. Br J Anaesth. 2014 Sep;113(3):402-9. doi: 10.1093/bja/aeu092. Epub 2014 Apr 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: July 30, 2013
• First Submitted That Met QC Criteria: July 31, 2013
• First Posted (Estimate): August 1, 2013

Study Record Updates

• Last Update Posted (Estimate): April 6, 2016
• Last Update Submitted That Met QC Criteria: April 4, 2016
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Total knee arthroplasty; Postoperative anemia; Iron therapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Anemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Trace Elements; Micronutrients; Glycine Agents; Glycine; Iron
• Other Study ID Numbers: FEV-POST/ESP10; 2010-023038-22 (EudraCT Number)