Intravenous Iron for Correction of Anaemia After Colorectal Surgery

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02999217
• Other study ID #: BEC-MF-74
• Status: Recruiting
• Phase: Phase 4
• First received: October 27, 2016
• Last updated: December 16, 2016
• Start date: October 2016
• Est. completion date: October 2018

Study information

• Verified date: December 2016
• Source: Kaunas University of Medicine
• Contact: Jurate Gudaityte, MDPhDAssProf
• Phone: +37069808531
• Email: jurate.gudaityte[@]kaunoklinikos.lt
• Is FDA regulated: No
• Health authority: Lithuania: Bioethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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.
• 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.

Locations

Country	Name	City	State
Lithuania	Department of Anaesthesiology, Lithuanian University of Health Sciences	Kaunas

Sponsors (3)

Lead Sponsor	Collaborator
Kaunas University of Medicine	Orivas, Lithuania, Pharmacosmos A/S

Country where clinical trial is conducted

Lithuania, 

References & Publications (8)

Cladellas M, Bruguera J, Comín J, Vila J, de Jaime E, Martí 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. — View Citation

Edna TH, Karlsen V, Jullumstrø 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. — View 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. Review. — View Citation

Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011 Apr 28;117(17):4425-33. doi: 10.1182/blood-2011-01-258467. Review. — View 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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of participants with perioperative complications	Total number of postoperative complications will be counted in both groups.	4 weeks after surgery	No
Secondary	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	No