Intravenous Iron for Correction of Anaemia After Colorectal Surgery

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Neoplasms; Anemia, Iron-Deficiency; Colorectal Surgery; Intravenous Drug Usage
• Intervention / Treatment: Drug: Iron isomaltoside; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jurate Gudaityte, MDPhDAssProf; Phone Number: +37069808531; Email: jurate.gudaityte@kaunoklinikos.lt
• Study Contact Backup: Name: Andrius Macas, MDPhDProf; Phone Number: +37068639123; Email: andrius.macas@kaunoklinikos.lt

Study Locations

• Lithuania
  • Kaunas, Lithuania, LT50009
    • Recruiting
    • Department of Anaesthesiology, Lithuanian University of Health Sciences
    • Contact: Jurate Gudaityte, MDPhDAssProf; Phone Number: +37069808531; Email: jurate.gudaityte@kaunoklinikos.lt
    • Contact: Andrius Macas, MDPhDProf; Phone Number: +37068639123; Email: andrius.macas@kaunoklinikos.lt
    • Sub-Investigator: Ruta Paskauskaite, student

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment; 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; 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.; Other Names: Monofer
Placebo Comparator: Control; The same amount of intravenous saline for patients with preoperative anaemia (Hb 90-120 g/l and plasma ferritin<100 mkg/l).	Drug: Saline; 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.; Other Names: Sodium chloride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kaunas University of Medicine
• Collaborators: Pharmacosmos A/S; Orivas, Lithuania
• Investigators: Study Chair: Andrius Macas, MDPhDProf, Head of the Department of Anaesthesiology, Medical academy, Lithuanian University of Health Sciences

Publications and helpful links

General Publications

• 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.
• Shander A, Knight K, Thurer R, Adamson J, Spence R. Prevalence and outcomes of anemia in surgery: a systematic review of the literature. Am J Med. 2004 Apr 5;116 Suppl 7A:58S-69S. doi: 10.1016/j.amjmed.2003.12.013.
• Edna TH, Karlsen V, Jullumstro E, Lydersen S. Prevalence of anaemia at diagnosis of colorectal cancer: assessment of associated risk factors. Hepatogastroenterology. 2012 May;59(115):713-6. doi: 10.5754/hge11479.
• Ward DG, Roberts K, Brookes MJ, Joy H, Martin A, Ismail T, Spychal R, Iqbal T, Tselepis C. Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol. 2008 Mar 7;14(9):1339-45. doi: 10.3748/wjg.14.1339.
• Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011 Apr 28;117(17):4425-33. doi: 10.1182/blood-2011-01-258467. Epub 2011 Feb 23.
• Leichtle SW, Mouawad NJ, Lampman R, Singal B, Cleary RK. Does preoperative anemia adversely affect colon and rectal surgery outcomes? J Am Coll Surg. 2011 Feb;212(2):187-94. doi: 10.1016/j.jamcollsurg.2010.09.013.
• Cladellas M, Bruguera J, Comin J, Vila J, de Jaime E, Marti J, Gomez M. Is pre-operative anaemia a risk marker for in-hospital mortality and morbidity after valve replacement? Eur Heart J. 2006 May;27(9):1093-9. doi: 10.1093/eurheartj/ehi830. Epub 2006 Mar 14.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: December 16, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: colorectal cancer; iron isomaltoside; plasma ferritin; haemoglobin
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Colorectal Neoplasms; Anemia, Iron-Deficiency; Anemia; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: BEC-MF-74

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study completion.