Postoperative i.v. Iron Substitution in Patients With Diagnosed Iron Deficiency

In this study, patients with confirmed and documented preoperative non-anaemic iron deficiency (diagnosis up to 28 days before surgery in routine pre-surgery monitoring) who develop anaemia within 12 to 72 hours after start of surgery (with additional confirmation at Baseline) and for whom fast replenishment of iron stores is necessary, will be included and substituted within 24h after Screening Visit/V1. Peri- or postoperative anaemia will be assessed as soon as possible but earliest 12 h after surgery. For short term safety analysis iron in urine will be measured in the first urine after the end of i.v. administration in the first 35 patients who are eligible for analysis in each i.v. treatment group. Only those patients are eligible for whom haematuria and/or proteinuria are excluded using dip stick test. The Ferric Carboxymaltose treatment arm will be closed if a sufficient number of patients is included for safety analysis.The study will then be continued for assessment of co-primary efficacy endpoint: The effectiveness of postoperative i.v. iron substitution with Polyglucoferron compared to conventional oral iron substitution with Ferrous sulfate (treatment 28 - 35 days) to normalize Hb-values or to increase Hb-values by at least 1.5 g/dl until visit 4 will be evaluated as well as patient related outcomes, such as the decreased need for allogenic blood transfusions. In addition, the well-being of the patient will be assumed to improve after treatment using the SF36 questionnaire.

Inclusion criteria

• Males or female; aged ≥ 18 years
• Patients after major surgery (e.g., orthopaedic/trauma, vascular, visceral, cardiac surgery) with risk of Hb reduction and/or blood loss who develop anaemia defined as haemoglobin of <12 g/dL for female and <13 g/dL for men within 12 to 72 h after start of surgery and with confirmation at Baseline
• Confirmed and documented preoperative iron deficiency defined as S-ferritin <100 ng/mL without anaemia (Hb ≥12 g/dL for female and ≥13 g/dL for male) within 28 days before surgery
• need for fast iron replenishment as judged by the treating physician
• Written informed consent; willing/able to comply with the protocol

Exclusion criteria

• Pregnancy in female patients or breastfeeding women
• Female patients not willing to use a safe method of contraception (PEARL index <1) for the full study period
• Severe physical inability, e.g., American society of anesthesiologists (ASA) physical status IV or V
• Patients receiving blood transfusion 24 week prior surgery
• Non-iron deficiency anaemia, e.g., known Vitamin B12 or folate deficiency, haemoglobinopathy, or unexplained anaemia
• Anticipated medical need for erythropoiesis-stimulating agents during the main study period
• Patients with hemodynamic instability due to any ongoing bleeding. Absence of ongoing bleeding will be confirmed determined either by decision of two independent physicians or by removal of drainage, whichever occurs earlier in routine care)
• Patients with any contraindication to the investigational products, e.g.,

• known sensitivity to iron or an ingredient of the investigational products
• Significant history of systemic allergic reactions
• Haemachromatosis, thalassemia or TSAT >50% as indicator of iron overload
• Acute or chronic intoxication
• Infection (patient on non-prophylactic antibiotics)
• Chronic liver disease and/or screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) above three times the upper limit of the normal range
• Chronic kidney disease, defined as Glomerular Filtration Rate (GFR) <30 mL/min
• Active uncontrolled immune-mediated diseases such as rheumatoid arthritis or inflammatory bowel disease
• Primary haematologic disease
• Drug or alcohol abuse according to WHO definition
• Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study
• Current or previous participation in another clinical trial during the last 90 days before screening
• Exclusion criteria related to Ferrous sulfate

• according to Summary of product characteristics (SmPC)
• hypersensitivity to any ingredient in the formulation
• concomitant parenteral iron
• haemochromatosis, and other iron overload syndromes
• Exclusion criteria related to Ferric Carboxymaltose:

• according to Summary of product characteristics (SmPC)
• hypersensitivity to the active substance, to Ferric Carboxymaltose or any of its excipients
• known serious hypersensitivity to other parenteral iron products
• anaemia not attributed to iron deficiency
• evidence of iron overload or disturbances in the utilisation of iron
• Exclusion criteria related to Polyglucoferron

• hypersensitivity to any ingredient in the formulation
• known serious hypersensitivity to other parenteral iron products
• anaemia not attributed to iron deficiency
• evidence of iron overload or disturbances in the utilisation of iron