IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia (IVICA)
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.
|Anemia Colorectal Neoplasm||Drug: Ferric carboxymaltose Drug: Ferrous Sulphate||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Study to Determine the Efficacy of Ferric Carboxymaltose in Preoperative Colorectal Cancer Related Anaemia, and to Develop Biomarkers to Predict Response to This Treatment Strategy|
- 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 [ Time Frame: 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.
- To determine differences in hemoglobin and hematinic markers between the groups. [ Time Frame: Enrollment to 6-12 weeks postoperatively ]Hematinic markers include ferritin, iron, transferrin, transferrin saturation, erythropoietin.
- To determine differences in hepcidin levels in relation to blood profile changes in participants in the intravenous group. [ Time Frame: 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 [ Time Frame: At point of operation only ]Iron transport proteins include DMT TFR1, Ferroportin, Ferritin. As acquired from examination of pathology tissue specimen excised.
- To determine differences in postoperative outcomes between the groups. [ Time Frame: Enrollment to 6-12 weeks postoperatively ]Post-operative outcomes include morbidity, mortality, length of stay.
- To determine differences in anemia symptomatology response between groups. [ Time Frame: Enrollment to 6-12 weeks postoperatively ]Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)
|Study Start Date:||April 2012|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
|Experimental: Ferric carboxymaltose||
Drug: Ferric carboxymaltose
A minimum of 1 dose of 1000mg of intravenous ferric carboxymaltose will be administered at least 14 days prior to the date of operation.
Other Name: Ferinject®
|Active Comparator: Ferrous Sulphate||
Drug: Ferrous Sulphate
(Control) 200mg twice a day of oral ferrous sulphate will be administered for a minimum of a two week period
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701310
|University Hospital Birmingham|
|Birmingham, West Midlands, United Kingdom, B15 2TH|
|Royal Wolverhampton Hospitals NHS Trust|
|Wolverhampton, West Midlands, United Kingdom, WV10 0QP|
|University Hospitals Bristol Foundation NHS Turst|
|Bristol, United Kingdom, BS2 8HW|
|Derby Hospital NHS Foundation Trust|
|Derby, United Kingdom, DE22 3NE|
|St James University Hospitals NHS Trust|
|Leeds, United Kingdom, LS9 7TF|
|University Hospitals of Leicester NHS Trust|
|Leicester, United Kingdom, LE1 5WW|
|Nottingham University Hospitals NHS Trust|
|Nottingham, United Kingdom, NG7 2UH|
|Yeovil District Hospital NHS Foundation Trust|
|Yeovil, United Kingdom, BA21 4AT|
|Study Chair:||Austin G Acheson, MBBS MD FRCS||Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery|