Clinical trial NCT01701310: IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anemia
Colorectal Neoplasm
Keywords: Adenocarcinoma
Anemia
Blood Transfusion
Colorectal surgery
Preoperative care
Perioperative care
Postoperative care
Iron
Hematinics
Hepcidin
Quality of life
Postoperative complications
Lead sponsor: Nottingham University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2012-10-05
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Diagnosed with histologically proven colorectal adenocarcinoma.
* Anemic at point of diagnosis of colorectal adenocarcinoma. (Haemoglobin values of \<12 g/dL for males and \<11 g/dL for females)
* Medically fit for surgery.
* Date of planned surgery is \>14 days from date of planned initiation of intervention (intravenous ferric carboxymaltose /oral ferrous sulphate).
* Able and willing to comply with all study requirements.
* Willing to allow his/her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion criteria:

* Female participants who are pregnant, lactating or planning a pregnancy during the course of the study.
* Previous gastric, small bowel or colorectal surgery (where ≥50% of stomach or terminal ileum has been resected)
* Current chemotherapeutic treatment.
* Known previous anaemia not attributable to colorectal carcinoma (i.e. anaemia in patients with well established inflammatory disorders or chronic renal disease).
* Known haematological disease.
* Features necessitating urgent surgery (e.g. obstructive symptoms).
* Previous allergy to intravenous iron or related iron products.
* Significant symptomatic anemia necessitating urgent transfusion (e.g. cardiovascular compromise)
* Patients who are unable to consent.
* Significant renal or hepatic impairment.
* -Donation of blood during the study.
* Participants who have participated in another research study involving an investigational product in the past 12 weeks
* Prisoners and minors (\<18 years)
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Primary outcomes:
measure: 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
timeFrame: 0 - 6 to 12 weeks
Secondary outcomes:
measure: To determine differences in hemoglobin and hematinic markers between the groups.
timeFrame: Enrollment to 6-12 weeks postoperatively
measure: To determine differences in hepcidin levels in relation to blood profile changes in participants in the intravenous group.
timeFrame: Enrollment to 6-12 weeks postoperatively.
measure: To determine differences in colonic mucosal expression of iron transport proteins, C-myc and NKD1 between the groups
timeFrame: At point of operation only
measure: To determine differences in postoperative outcomes between the groups.
timeFrame: Enrollment to 6-12 weeks postoperatively
measure: To determine differences in anemia symptomatology response between groups.
timeFrame: Enrollment to 6-12 weeks postoperatively
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
state: West Midlands
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton Hospitals NHS Trust
state: West Midlands
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol Foundation NHS Turst
city: Derby
country: United Kingdom
facility: Derby Hospital NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: St James University Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital NHS Foundation Trust
Study officials:
affiliation: Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery
name: Austin G Acheson, MBBS MD FRCS
role: STUDY_CHAIR
References: