IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia

Phase 4

Completed

• Conditions: Anemia; Colorectal Neoplasm
• Interventions: Drug: Ferrous Sulphate; Drug: Ferric carboxymaltose

• Registration Number: NCT01701310
• Lead Sponsor: Nottingham University Hospitals NHS Trust

Brief Summary

116 eligible patients with confirmed non-metastatic colorectal adenocarcinoma and anemia will be randomized to receive either oral ferrous sulphate (control) or intravenous ferric carboxymaltose (intervention).

It is hypothesized that intravenous iron supplementation is more efficacious than oral iron therapy.

Detailed Description

Patients who are anemic at the time of operation have been shown to have an increased frequency of complications including wound infection and longer post-operative admissions. Similarly, patients who are anemic at the time of their cancer operation are more likely to require a blood transfusion which may increase the risk of recurrence of the cancer.

At present, oral iron is often used to treat anemia preoperatively in an attempt to minimize the risk above. This drug is often poorly tolerated due to the side effect profile. Blood transfusions can also be administered but expose the patient to other risks including infection and transfusion associated reactions. In order to overcome these issues, intravenous iron preparations have been developed and have improved in safety.

This is a multi-center, randomized, open label clinical trial, which looks to investigate the efficacy of intravenous iron is in the treatment of preoperative anemia in colorectal patients. Patients will be randomized to receive intravenous ferric carboxymaltose (treatment group) or oral ferrous sulphate (control). The outcomes reviewed will include the amount and frequency of blood transfusions received, changes in patient blood profiles, patient quality of life scores, operative complications and hospital length of stay. The role of hepcidin as a biomarker of treatment response will also be assessed.

The primary hypothesis to be tested is that intravenous iron will decrease transfusion rates. To detect a significant clinical difference in blood transfused consistent with previous published data (1 unit), 58 patients will be required in each arm of the study with 90% power (alpha 0.05).

Randomization will be performed independently to the trial team using a computer generated variable block randomization program.

All data will be confidentially recorded on a Case Report Form, as will drug reactions and side effects.

Study Timeline

• Study First Submitted: 2012-03-21
• Study Start: 2012-04
• Study First Submitted QC: 2012-10-03
• Study First Posted: 2012-10-05
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-27
• Last Update Posted: 2016-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ferrous Sulphate	Ferrous Sulphate	-
Ferric carboxymaltose	Ferric carboxymaltose	-

Primary Outcome Measures

Name	Time	Method
To determine if the use of intravenous ferric carboxymaltose can reduce the need for allogeneic blood transfusion compare to oral ferrous sulphate in patients with colorectal adenocarcinoma related anaemia	0 - 6 to 12 weeks	To investigate if the number of units transfused per participant, the number of participants whom receive a blood transfusion and the total number of units of blood transfused differs between the two study arms. This period monitored will begin at enrolment into the study, and cease at review in outpatient clinic 6 - 12 weeks post operatively.

Secondary Outcome Measures

Name	Time	Method
To determine differences in hemoglobin and hematinic markers between the groups.	Enrollment to 6-12 weeks postoperatively	Hematinic markers include ferritin, iron, transferrin, transferrin saturation, erythropoietin.
To determine differences in postoperative outcomes between the groups.	Enrollment to 6-12 weeks postoperatively	Post-operative outcomes include morbidity, mortality, length of stay.
To determine differences in anemia symptomatology response between groups.	Enrollment to 6-12 weeks postoperatively	Quality of Life questionnaires will be used (SF-36\[short form 36\] and EQ-5D)
To determine differences in hepcidin levels in relation to blood profile changes in participants in the intravenous group.	Enrollment to 6-12 weeks postoperatively.	To review the use of hepcidin as a biomarker to predict response to therapy.
To determine differences in colonic mucosal expression of iron transport proteins, C-myc and NKD1 between the groups	At point of operation only	Iron transport proteins include DMT TFR1, Ferroportin, Ferritin. As acquired from examination of pathology tissue specimen excised.

Trial Locations

Locations (8)

University Hospital Birmingham; 🇬🇧 Birmingham, West Midlands, United Kingdom

Royal Wolverhampton Hospitals NHS Trust; 🇬🇧 Wolverhampton, West Midlands, United Kingdom

St James University Hospitals NHS Trust; 🇬🇧 Leeds, United Kingdom

University Hospitals of Leicester NHS Trust; 🇬🇧 Leicester, United Kingdom

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, United Kingdom

Yeovil District Hospital NHS Foundation Trust; 🇬🇧 Yeovil, United Kingdom

University Hospitals Bristol Foundation NHS Turst; 🇬🇧 Bristol, United Kingdom

Derby Hospital NHS Foundation Trust; 🇬🇧 Derby, United Kingdom