Efficacy of Preoperative Intravenous Iron in Anaemic Colorectal Cancer Surgical Patients

Efficacy of Preoperative Intravenous Iron Isomaltoside in Colorectal Cancer Surgical Patients With Iron Deficiency Anaemia Compared to Standard Care: a Pilot Randomized Controlled Trial

Iron deficiency anaemia is a common condition among colorectal surgical patient. Untreated anaemia would lead to increase in blood transfusion, surgical complications and mortality. Treatment with oral iron sulphate is poorly tolerated due to side effects. Intravenous iron supplement provides an alternative way to rapidly replace iron deficit during the preoperative period among surgical patients. Evidence is growing for its effect in rising hemoglobin level and reducing blood transfusion, at the same time supporting its safety profile.

The investigators plan for a single-centered, randomized controlled trial to examine the effect of intravenous iron compared to standard care in terms of hemoglobin level/serum ferritin increment, need for blood transfusion, duration of hospital stay, quality of recovery and surgical complication rate, as well as safety profile among colorectal cancer surgical patients in Hong Kong. The investigator propose the following pilot RCT for exploring the effect size and study process in conducting the above-mentioned large-scale RCT.

Study Overview

• Status: Completed
• Conditions: Anemia, Iron-Deficiency; Colorectal Cancer
• Intervention / Treatment: Drug: iron isomaltoside(Monofer®)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital

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:

• Age >18 years old with written informed consent
• Anaemia defined as: hemoglobin concentration < 13g/dL (same cut-off for both male and female patients according to the International consensus statement on the perioperative management of anaemia and iron deficiency)2
• Laboratory test confirmed iron deficiency: serum ferritin <30mcg/L alone or serum ferritin 30-100mcg/L with TSAT < 20%

Exclusion Criteria:

• Pregnancy or lactation
• Other known causes of anaemia apart from iron deficiency: untreated B12/folate deficiency, hemolytic disease, hemoglobinopathy/thalassemia, chronic renal failure on dialysis
• Presence of iron overload (serum ferritin > 300g/dL or TSAT > 50%); known hemochromatosis
• Previous or ongoing iron replacement/use of erythropoietin within 12 weeks before recruitment
• Known hypersensitivity towards iron isomaltoside
• Significant liver function derangement (AST/ALP exceeding three times upper limit of normal range)
• Participation in another ongoing interventional clinical trial(s)
• Patients with less than 3 weeks waiting time to surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Treatment arm; intravenous iron isomaltose 3-10 weeks before operation date. The dose will be determined by the patient's body weight: > 50kg: 1000mg; <50kg: 20mg/kg body weight, to be infused over 30 minutes. 2 weeks after intravenous iron isomaltoside administration, blood test for hemoglobin level and iron profile would be repeated. Subjects with hemoglobin level less than 10g/dL will receive a second dose of intravenous iron isomaltoside. The second dose would be identical to the first dose	Drug: iron isomaltoside(Monofer®); intravenous iron isomaltoside
NO_INTERVENTION: Control arm; Patient randomized to the control arm will follow the standard perioperative care and the perioperative management they received will be identical to the treatment arm except no intravenous iron isomaltoside will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative change in hemoglobin concentration (g/dL)	the difference between the value at diagnosis(baseline) and preoperative day (3-10weeks after diagnosis).	3 weeks to 10 weeks
Preoperative change in serum ferritin (mcg/L)	the difference between the value at diagnosis(baseline) and preoperative day (3-10weeks after diagnosis).	3 weeks to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Units of red blood cells transfused in perioperative period	Units of red blood cells transfused from diagnosis to discharge	3 weeks to 12 weeks
Duration of hospital stay (days)		1 days up to 1 month
Quality of recovery as measured by questionnaire (QoR-15(Chinese))		post op day 3
Incidence of adverse reactions/serious adverse events to intravenous iron administration and adverse reaction to blood transfusions		up to post op day 30
Rate of surgical complications	recorded and graded according to Clavien Classification of Surgical Complications	up to post op day 30
Days (alive and) at home within 30 days of surgery (DAH30)		up to post op day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient recruitment rate(%)	number of recruited patients divided by number of eligible patients x 100%	through study completion, an average of 1 year
Number of patients recruited per month		through study completion, an average of 1 year
Median waiting time to surgery (days)		through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Prince of Wales Hospital, Shatin, Hong Kong

Publications and helpful links

General Publications

• Fung PLP, Lau VNM, Ng FF, Leung WW, Mak TWC, Lee A. Perioperative changes in haemoglobin and ferritin concentrations from preoperative intravenous iron isomaltoside for iron deficiency anaemia in patients with colorectal cancer: A pilot randomised controlled trial. PLoS One. 2022 Jun 30;17(6):e0270640. doi: 10.1371/journal.pone.0270640. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2018
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): June 30, 2020

Study Registration Dates

• First Submitted: May 28, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (ACTUAL): June 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 17, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Patient blood management
• 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: NTEC-2018-0169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No