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 (CABG-01)

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

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

Study Overview

• Status: Completed
• Conditions: Non-anaemic Patients Undergoing Cardiac Surgery
• Intervention / Treatment: Drug: Iron isomaltoside 1000 (Monofer®); Drug: Natriumklorid 9 mg/ml, Fresenius Kabi

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark

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:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Iron isomaltoside 1000 (Monofer®); Iron isomaltoside 1000 (Monofer®) - Intravenous Infusion	Drug: Iron isomaltoside 1000 (Monofer®); All subjects randomised to this group will receive 1000 mg iron isomaltoside 1000 as a single dose infusion administered over 15 minutes
Placebo Comparator: 0,9% sodium saline; Placebo (0.9% sodium saline) - Intravenous infusion	Drug: Natriumklorid 9 mg/ml, Fresenius Kabi; All subjects randomised to this group will receive an infusion of 100 ml 0.9% sodium chlorid administered over 15 min.; Other Names: 0.9% sodium chlorid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in haemoglobin (Hb) concentrations	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	From t=0 to t=4 weeks postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb concentrations	Proportion of patients that are anaemic (women < 12 g/dL and men < 13 g/dL) at day 5 and week 4	t=0, t=5 days and t=4 weeks
Number of patients in each randomisation group who need blood transfusion and number of transfusions administered	To compare the number of patients who will need blood transfusion and number of transfusions in each randomisation group	From t=0 to t=day 5 and t=4 weeks
Change in concentrations of serum ferritin, serum iron and Transferrin Saturation (TfS) TfS, and reticulocytes	From t=0 to t=day 5 and t=4 weeks	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
Number of postoperative days to discharge	To compare the number of days to discharge between the 2 randomisation groups	From t=0 to discharge
Changes in New York Heart Association (NYHA) classification	To compare the changes in New York Heart Association (NYHA) classification from baseline to 4 weeks postoperatively	From t=0 to t=4 weeks
Number of patients in each randomisation group who experience any study drug related adverse events (AEs/SAEs/SUSARs)	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	From screening and until completion (t=-7 day and upto t=4 weeks)
Change in Hb	Proportion of patients able to maintain Hb between 9.5 and 12.5 g/dL (both values included) at day 5 and week 4	t=0, t=day 5 and t=week 4

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S
• Collaborators: CRO Max Neeman
• Investigators: Study Chair: Lars Lykke Thomsen, Pharmacosmos A/S

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: March 16, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 27, 2012

Study Record Updates

• Last Update Posted (Estimate): April 29, 2014
• Last Update Submitted That Met QC Criteria: April 28, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Cardiac surgery; Anaemia
• Additional Relevant MeSH Terms: Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: P-Monofer-CABG-01