A Prospective, Comparative Study of Intravenous Iron Isomaltoside 1000 (Monofer®) Administered by Infusions to Anaemic Patients Undergoing Elective or Sub-Acute Coronary Artery Bypass Graft, Valve Replacement or a Combination Thereof (CABG-01)

• Change in Hb concentrations [ Time Frame: From t=0 to to t=3 months postoperatively ] [ Designated as safety issue: No ]
  To compare the change in Hb concentrations from baseline to 3 months postoperatively
• Number of patients in each randomisation group who need blood transfusion and number of transfusions administered [ Time Frame: From t=0 to t=4 weeks and t=3 months ] [ Designated as safety issue: No ]
  To compare the number of patients who will need blood transfusion and number of transfusions in each randomisation group
• Change in concentrations of serum ferritin, serum iron and Transferrin Saturation (TfS) TfS, and reticulocytes [ Time Frame: Change from baseline (preoperatively- the day before surgery or same day) in concentrations of serum ferritin, serum iron and Transferrin Saturation (TfS) TfS, and reticulocytes at 4 weeks and 3 months postoperatively ] [ Designated as safety issue: No ]
  From t=0 to t=4 weeks and t=3 months postoperatively
• Number of postoperative days to discharge [ Time Frame: From t=0 to discharge ] [ Designated as safety issue: No ]
  To compare the number of days to discharge between the 2 randomisation groups
• Changes in six-minute walking distance [ Time Frame: From t=0 to t=4 weeks ] [ Designated as safety issue: No ]
  To compare the changes in six-minute walking distance from baseline to 4 weeks post operatively between the 2 groups
• Number of patients in each randomisation group who experience any study drug related adverse events (AEs/SAEs/SUSARs) [ Time Frame: t= -7 days ] [ Designated as safety issue: Yes ]
  To compare the number of study drug related adverse events (AEs/SAEs/SUSARs) between subjects treated with iron isomaltoside 1000 (Monofer®) infusion and subjects treated with placebo infusion

The purpose of the study is to demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is superior compared to placebo with respect to increasing the haemoglobin level in preoperative anaemic patients undergoing cardiac surgery

The role of preoperative haemoglobin as a predictor of short-term and long-term outcomes after cardiac surgery has been well established. Anaemia can impede a patient's ability to recover fully and participate in postoperative rehabilitation. Preoperative treatment of anaemic patients undergoing cardiac surgery is essential to reduce the risk of postoperative complications due to loss of haemoglobin. To date, no prospective randomised clinical study in cardiac surgery assessing the effect of preoperative intravenous iron supplementation in patients undergoing cardiac surgery has been reported. This prospective, randomized, placebo controlled, double blind study is planned to evaluate the effect of intravenous iron isomaltoside 1000 (Monofer®) in comparison with placebo in preoperative anaemic patients undergoing cardiac surgery.

• Drug: Iron isomaltoside 1000 (Monofer®)

  Full iron replacement dose of iron isomaltoside 1000 (Monofer®) for the individual subject is calculated according to the formula below:

  Total iron deficit (mg) = body weight (kg) x (targeted Hb-actual Hb) (g/dl) x 2.4 + depot iron (mg) Depot iron: 500 mg Suggested target Hb: Female: 13.0 g/dl (8,1 mmo/l), Male: 14,0 g/dl (8,7 mmol/l)

  Other Name: Iron isomaltoside 1000 (Monofer®)
• Drug: Natriumklorid 9 mg/ml, Fresenius Kabi
  0.9% sodium chlorid. Same calculation as for active comparator will be used to calculate number of ml
  Other Names:

  • Natriumklorid 9 mg/ml, Fresenius Kabi
  • 0.9% sodium chlorid.

• Active Comparator: Iron isomaltoside 1000 (Monofer®)
  Iron isomaltoside 1000 (Monofer®) - Intravenous Infusion
  Intervention: Drug: Iron isomaltoside 1000 (Monofer®)
• Placebo Comparator: 0,9% sodium saline
  Placebo (0.9% sodium saline) - Intravenous infusion
  Intervention: Drug: Natriumklorid 9 mg/ml, Fresenius Kabi

Inclusion Criteria:

1. Men and women, aged more than 18 years.
2. Anaemic patients undergoing elective or sub-acute CABG, valve replacement or a combination thereof.
3. Female Hb < 11.5 g/dl (7.1 mmol/L), Male Hb < 13,0 g/dl (8.1 mmol/L).
4. Willingness to participate after informed consent.

Exclusion Criteria:

1. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis).
2. Serum Ferritin > 800 ng/ml.
3. Known hypersensitivity to any excipients in the investigational drug products.
4. Patients with a history of multiple allergies.
5. Decompensated liver cirrhosis and hepatitis.
6. Alanine Aminotransferase (ALT) > 3 times normal upper value.
7. Acute infections (assessed by clinical judgement).
8. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
9. Pregnant or nursing. (To avoid pregnancy, women have to be postmenopausal (at least 12 months must have elapsed since last menstruation), surgically sterile, or women of child bearing potential must use one of the following contraceptives during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product: Contraceptive pills, Intrauterine Devices (IUD), contraceptive depot injections (prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches).
10. Participation in any other clinical trial where the study drug has not passed five half-lives prior to screening.
11. Untreated Vitamin B12 or folate deficiency.
12. Other IV or oral iron treatment within 4 weeks prior to screening visit.
13. Erythrypoietin treatment within 4 weeks prior to screening visit
14. Impaired renal function defined by se-creatinin > 150 µmol/l