Clinical trial NCT02999217: Intravenous Iron for Correction of Anaemia After Colorectal Surgery
Official title: The Impact of Treatment of Anaemia With Intravenous Iron on Haematological Values for Patients After Colorectal Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anemia, Iron-Deficiency
Intravenous Drug Usage
Colorectal Neoplasms
Colorectal Surgery
Keywords: iron isomaltoside
plasma ferritin
haemoglobin
colorectal cancer
Lead sponsor: Kaunas University of Medicine
Sponsor class: OTHER
Collaborators: name: Orivas, Lithuania
name: Pharmacosmos A/S
First posted: 2016-12-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 4-week prospective double blind anaemia management study evaluates the effect of high-dose postoperative intravenous iron vs placebo for patients after colorectal cancer surgery. Patients with preoperative levels of haemoglobin 90-120 g/l will be randomly assigned to receive either 1 g of intravenous iron or equal amount of saline postoperatively. Comparison will be based on the levels of haemoglobin, ferritin and other haematological parameters over time and profile of clinical recovery.

The primary end point is that iron isomaltoside given postoperatively is superior to placebo in terms of increase and stability of levels of haemoglobin and other haematological parameters.

Detailed description: The Aim: to assess the effect of treatment of preoperative anaemia with intravenous iron on haematological parameters for patients after elective colorectal surgery.

Primary Hypothesis: postoperative treatment with intravenous iron increases the levels of haemoglobin, ferritin, red cell count and is superior compared to placebo.

Secondary effects: treatment with intravenous iron vs placebo provides reduction of blood transfusions, postoperative complications and hospital stay.

The Objectives:

1. To estimate the rate of preoperative anaemia in patients of elective colorectal surgery.
2. To assess the dynamic changes of total blood count values in colorectal surgery patients treated with postoperative intravenous iron.
3. To compare the changes in total blood count values over time in colorectal surgery patients treated with intravenous iron versus colorectal surgery patients of the control group.

Methods:

The prospective, double-blinded study includes American Society of Anaesthesiology (ASA) I-III patients, aged 18-75 years, admitted for elective colorectal surgery. Preoperatively, patients with levels of haemoglobin 90-120 g/l will be identified and their serum ferritin will be tested. In cases of ferritin\<100 mkg/l, patients will be blindly randomized into one of the two groups: treatment group (group T) is given 1000 mg of intravenous iron (iron isomaltoside, Orivas, Pharmacosmos) in the postoperative recovery ward and control group (group C) which is given the same volume of intravenous saline (placebo).

Patients in both groups will be provided with general anaesthesia (fentanyl, propofol, atracurium, inhaled sevoflurane for maintenance) and after tracheal extubation will be transferred to the recovery ward.

Patient blood tests: total blood count, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), plasma ferritin) will be assessed in both groups 1 day preoperatively, day 1 and 3 postoperatively, the day of discharge and 4 weeks after discharge from the department of surgery. The level of reticulocyte and reticulocyte haemoglobin concentration will be determined on the day of discharge and 4 weeks after discharge.

According to the study protocol, groups will also be compared in terms of clinical recovery, requirements of intravenous fluids and blood transfusion and duration of hospital stay.

Eligibility criteria: Inclusion Criteria:

* elective colorectal cancer surgery
* preoperative haemoglobin 90-120 g/l
* preoperative plasma ferritin \<100 mkg/l

Exclusion Criteria:

* laparoscopic colorectal surgery
* body mass \<50kg
* history of overdosage of iron products
* family history of haemochromatosis, thalassaemia,
* non-iron deficiency anaemia (Vit. B12, folic acid defficiency, haemoglobinopathies)
* under treatment with erythropoietin, intravenous iron or blood transfusion in the last 12 weeks
* allergy to iron carboxymaltose or its supplements
* body temperature \> 37.5 °C or under antibiotic use
* chronic liver diseases or/and increased levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times over normal upper limit
* patients ill with grave bronchial asthma
* patients with manifestation of allergy

Primary outcomes:
measure: Changes in haemoglobin level
timeFrame: 4 weeks after surgery
Secondary outcomes:
measure: Changes of plasma ferritin
timeFrame: 4 weeks after surgery
measure: Changes of red blood cell count
timeFrame: 4 weeks after surgery
measure: Changes of mean corpuscular volume
timeFrame: 4 weeks after surgery
measure: Changes of mean corpuscular haemoglobin concentration
timeFrame: 4 weeks after surgery
measure: Changes of reticulocyte count
timeFrame: 4 weeks after surgery
measure: Changes of reticulocyte haemoglobin count
timeFrame: 4 weeks after surgery
measure: Rate of blood transfusion
timeFrame: From date of randomization until the day of discharge from the hospital, up to 2 weeks after surgery
measure: Amount of intravenous fluid therapy
timeFrame: From date of randomization until the day of discharge, up to 2 weeks after surgery
measure: Number of participants with perioperative complications
timeFrame: 4 weeks after surgery
measure: Duration of hospital stay
timeFrame: From the date of randomization until the day of discharge, up to 2 weeks after surgery
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Department of Anaesthesiology, Lithuanian University of Health Sciences
Study officials:
affiliation: Head of the Department of Anaesthesiology, Medical academy, Lithuanian University of Health Sciences
name: Andrius Macas, MDPhDProf
role: STUDY_CHAIR
References:
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citation: Hogan M, Klein AA, Richards T. The impact of anaemia and intravenous iron replacement therapy on outcomes in cardiac surgery. Eur J Cardiothorac Surg. 2015 Feb;47(2):218-26. doi: 10.1093/ejcts/ezu200. Epub 2014 May 13.
citation: Elhenawy AM, Meyer SR, Bagshaw SM, MacArthur RG, Carroll LJ. Role of preoperative intravenous iron therapy to correct anemia before major surgery: study protocol for systematic review and meta-analysis. Syst Rev. 2015 Mar 15;4:29. doi: 10.1186/s13643-015-0016-4.