Clinical trial NCT01563367: A Prospective, Comparative Study of Intravenous Iron Isomaltoside 1000 (Monofer®) Administered by Infusions to Non-Anaemic Patients Undergoing Elective or Sub-Acute Coronary Artery Bypass Graft, Valve Replacement or a Combination Thereof
Official title: A Randomized, Prospective, Double-Blind, Comparative Placebo-Controlled Study of Intravenous Iron Isomaltoside 1000 (Monofer®) Administered by Infusions to Non-Anaemic Patients Undergoing Elective or Sub-Acute CABG, Valve Replacement or a Combination Thereof
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-anaemic Patients Undergoing Cardiac Surgery
Keywords: Anaemia
Cardiac surgery
Lead sponsor: Pharmacosmos A/S
Sponsor class: INDUSTRY
Collaborators: name: CRO Max Neeman
First posted: 2012-03-27
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 non-anaemic patients undergoing cardiac surgery

Detailed description: 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. It has been found that patients with a normal haemoglobin level may become anaemic during surgery. An evaluation of patients undergoing cardiac surgery, i.e. CABG, valve or combined CABG-valve procedures showed that there was a decrease in mean haemoglobin level pre-surgery two and four days after surgery. To date, no prospective randomised clinical study in cardiac surgery assessing the effect of 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 non-anaemic patients undergoing cardiac surgery.

Eligibility criteria: Inclusion Criteria:

1. Men and women, aged more than 18 years.
2. Subjects undergoing elective or sub-acute CABG, valve replacement or a combination thereof
3. Female Hb ≥ 12.0 g/dl (7.45 mmol/l), Male Hb ≥ 13.0 g/dl (8.1 mmol/l).
4. Willingness to participate after informed consent.

Exclusion Criteria:

1. Subjects receiving blood transfusion less than 30 days before screening and/or during the elective or sub-acute CABG, valve replacement, or a combination thereof.
2. Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis).
3. Serum Ferritin \> 800 ng/ml.
4. Known hypersensitivity to any excipients in the investigational drug products.
5. Patients with a history of multiple allergies.
6. Decompensated liver cirrhosis and hepatitis.
7. Alanine Aminotransferase (ALT) \> 3 times normal upper value.
8. Acute infections (assessed by clinical judgement).
9. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
10. 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).
11. Participation in any other clinical trial where the study drug has not passed five half-lives prior to screening.
12. Untreated Vitamin B12 or folate deficiency.
13. Other IV or oral iron treatment within 4 weeks prior to screening visit.
14. Erythropoietin treatment within 4 weeks prior to screening visit
15. Impaired renal function defined by se-creatinin \> 150 µmol/l

Primary outcomes:
measure: Change in haemoglobin (Hb) concentrations
timeFrame: From t=0 to t=4 weeks postoperatively
Secondary outcomes:
measure: Change in Hb concentrations
timeFrame: t=0, t=5 days and t=4 weeks
measure: Number of patients in each randomisation group who need blood transfusion and number of transfusions administered
timeFrame: From t=0 to t=day 5 and t=4 weeks
measure: Change in concentrations of serum ferritin, serum iron and Transferrin Saturation (TfS) TfS, and reticulocytes
timeFrame: 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
measure: Number of postoperative days to discharge
timeFrame: From t=0 to discharge
measure: Changes in New York Heart Association (NYHA) classification
timeFrame: From t=0 to t=4 weeks
measure: Number of patients in each randomisation group who experience any study drug related adverse events (AEs/SAEs/SUSARs)
timeFrame: From screening and until completion (t=-7 day and upto t=4 weeks)
measure: Change in Hb
timeFrame: t=0, t=day 5 and t=week 4
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
Study officials:
affiliation: Pharmacosmos A/S
name: Lars Lykke Thomsen
role: STUDY_CHAIR
References: