Intravenous Iron for Correction of Anaemia After Colorectal Surgery

Study Overview
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Brief Summary
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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
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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: To estimate the rate of preoperative anaemia in patients of elective colorectal surgery. To assess the dynamic changes of total blood count values in colorectal surgery patients treated with postoperative intravenous iron. 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.

Official Title
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The Impact of Treatment of Anaemia With Intravenous Iron on Haematological Values for Patients After Colorectal Surgery

Conditions
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Anemia, Iron-Deficiency, Intravenous Drug Usage, Colorectal Neoplasms, Colorectal Surgery

Intervention / Treatment
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* Drug: Iron isomaltoside
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>1 g of intravenous iron isomaltoside given postoperatively for patients with preoperative anaemia (Hb 90-120 g/l and plasma ferritin<100 mkg/l). | Drug: Iron isomaltoside<br>* Intravenous injection 1 g given postoperatively in the recovery ward. Blood tests including red blood cell count, plasma ferritin, haemoglobin, haematocrit, mean corpuscular volume, mean haemoglobin concentration are made 1 day preoperatively, day 1, day 3 postoperatively, day of discharge and 1 month after discharge. Reticulocyte count and reticulocyte haemoglobin concentration tests are made on the day of discharge and 1 month after discharge. Count of total consumption of intravenous blood products. Count of total intravenous fluids. Clinical recovery and complications. Duration of hospital stay.<br>* Other names: Monofer;|
| Placebo Comparator: Control<br>The same amount of intravenous saline for patients with preoperative anaemia (Hb 90-120 g/l and plasma ferritin<100 mkg/l). | Drug: Saline<br>* Intravenous injection given postoperatively in the recovery ward. Blood tests including red blood cell count, plasma ferritin, haemoglobin, haematocrit, mean corpuscular volume, mean haemoglobin concentration are made 1 day preoperatively, day 1, day 3 postoperatively, day of discharge and 1 month after discharge. Reticulocyte count and reticulocyte haemoglobin concentration tests are made on the day of discharge and 1 month after discharge. Count of total consumption of intravenous blood products. Count of total intravenous fluids. Clinical recovery and complications. Duration of hospital stay.<br>* Other names: Sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in haemoglobin level | Haemoglobin level will be tested in both groups at day 1, 3 postoperatively, day of discharge and 4 weeks after surgery | 4 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of plasma ferritin | Other haematological variables will be tested in both groups at day 1, 3 postoperatively, day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Changes of red blood cell count | Other haematological variables will be tested in both groups at day 1, 3 postoperatively, day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Changes of mean corpuscular volume | Other haematological variables will be tested in both groups at day 1, 3 postoperatively, day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Changes of mean corpuscular haemoglobin concentration | Other haematological variables will be tested in both groups at day 1, 3 postoperatively, day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Changes of reticulocyte count | It will be tested in both groups at the day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Changes of reticulocyte haemoglobin count | It will be tested in both groups at the day of discharge and 4 weeks after surgery | 4 weeks after surgery | 
| Rate of blood transfusion | Total amount of blood transfusion units will be counted 2 weeks after surgery in both groups. | From date of randomization until the day of discharge from the hospital, up to 2 weeks after surgery | 
| Amount of intravenous fluid therapy | Total amount of intravenous fluids will be counted starting from the date of randomization, separately in the operating room, recovery area and each day postoperatively until 2 weeks after surgery in both groups. | From date of randomization until the day of discharge, up to 2 weeks after surgery | 
| Number of participants with perioperative complications | Total number of postoperative complications will be counted in both groups. | 4 weeks after surgery | 
| Duration of hospital stay | It will be counted in both groups 2 weeks after surgery in both groups. | From the date of randomization until the day of discharge, up to 2 weeks after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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haemoglobin, iron isomaltoside, plasma ferritin, colorectal cancer