search
Back to results

IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia (IVICA)

Primary Purpose

Anemia, Colorectal Neoplasm

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Ferric carboxymaltose
Ferrous Sulphate
Sponsored by
Nottingham University Hospitals NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring Adenocarcinoma, Anemia, Blood Transfusion, Colorectal surgery, Preoperative care, Perioperative care, Postoperative care, Iron, Hematinics, Hepcidin, Quality of life, Postoperative complications

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital Birmingham
  • Royal Wolverhampton Hospitals NHS Trust
  • University Hospitals Bristol Foundation NHS Turst
  • Derby Hospital NHS Foundation Trust
  • St James University Hospitals NHS Trust
  • University Hospitals of Leicester NHS Trust
  • Nottingham University Hospitals NHS Trust
  • Yeovil District Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ferric carboxymaltose

Ferrous Sulphate

Arm Description

Outcomes

Primary Outcome Measures

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
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

To determine differences in hemoglobin and hematinic markers between the groups.
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.
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
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.
Post-operative outcomes include morbidity, mortality, length of stay.
To determine differences in anemia symptomatology response between groups.
Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)

Full Information

First Posted
March 21, 2012
Last Updated
October 27, 2016
Sponsor
Nottingham University Hospitals NHS Trust
Collaborators
National Institute for Health Research, United Kingdom
search

1. Study Identification

Unique Protocol Identification Number
NCT01701310
Brief Title
IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia
Acronym
IVICA
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

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nottingham University Hospitals NHS Trust
Collaborators
National Institute for Health Research, United Kingdom

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Colorectal Neoplasm
Keywords
Adenocarcinoma, Anemia, Blood Transfusion, Colorectal surgery, Preoperative care, Perioperative care, Postoperative care, Iron, Hematinics, Hepcidin, Quality of life, Postoperative complications

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
116 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ferric carboxymaltose
Arm Type
Experimental
Arm Title
Ferrous Sulphate
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Other Intervention Name(s)
Ferinject®
Intervention Description
A minimum of 1 dose of 1000mg of intravenous ferric carboxymaltose will be administered at least 14 days prior to the date of operation.
Intervention Type
Drug
Intervention Name(s)
Ferrous Sulphate
Intervention Description
(Control) 200mg twice a day of oral ferrous sulphate will be administered for a minimum of a two week period
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
0 - 6 to 12 weeks
Secondary Outcome Measure Information:
Title
To determine differences in hemoglobin and hematinic markers between the groups.
Description
Hematinic markers include ferritin, iron, transferrin, transferrin saturation, erythropoietin.
Time Frame
Enrollment to 6-12 weeks postoperatively
Title
To determine differences in hepcidin levels in relation to blood profile changes in participants in the intravenous group.
Description
To review the use of hepcidin as a biomarker to predict response to therapy.
Time Frame
Enrollment to 6-12 weeks postoperatively.
Title
To determine differences in colonic mucosal expression of iron transport proteins, C-myc and NKD1 between the groups
Description
Iron transport proteins include DMT TFR1, Ferroportin, Ferritin. As acquired from examination of pathology tissue specimen excised.
Time Frame
At point of operation only
Title
To determine differences in postoperative outcomes between the groups.
Description
Post-operative outcomes include morbidity, mortality, length of stay.
Time Frame
Enrollment to 6-12 weeks postoperatively
Title
To determine differences in anemia symptomatology response between groups.
Description
Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)
Time Frame
Enrollment to 6-12 weeks postoperatively

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Austin G Acheson, MBBS MD FRCS
Organizational Affiliation
Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Birmingham
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Royal Wolverhampton Hospitals NHS Trust
City
Wolverhampton
State/Province
West Midlands
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
Facility Name
University Hospitals Bristol Foundation NHS Turst
City
Bristol
ZIP/Postal Code
BS2 8HW
Country
United Kingdom
Facility Name
Derby Hospital NHS Foundation Trust
City
Derby
ZIP/Postal Code
DE22 3NE
Country
United Kingdom
Facility Name
St James University Hospitals NHS Trust
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
University Hospitals of Leicester NHS Trust
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Yeovil District Hospital NHS Foundation Trust
City
Yeovil
ZIP/Postal Code
BA21 4AT
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia

We'll reach out to this number within 24 hrs