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IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Nottingham University Hospitals NHS Trust
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01701310
First received: March 21, 2012
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Anemia
Colorectal Neoplasm
Drug: Ferric carboxymaltose
Drug: Ferrous Sulphate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Nottingham University Hospitals NHS Trust:

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 [ Time Frame: 0 - 6 to 12 weeks ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Enrollment to 6-12 weeks postoperatively ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)


Estimated Enrollment: 116
Study Start Date: April 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01701310

Contacts
Contact: Barrie D Keeler, BSc FRCS 0115 8231145 barriekeeler@doctors.org.uk
Contact: Austin G Acheson, MD FRCS 0115 8231147 austin.acheson@nottingham.ac.uk

Locations
United Kingdom
University Hospital Birmingham Recruiting
Birmingham, West Midlands, United Kingdom, B15 2TH
Contact: Thomas Pinkney, FRCS       Thomas.Pinkney@uhb.nhs.uk   
Contact: Mandip Narewal       Mandip.Narewal@uhb.nhs.uk   
Royal Wolverhampton Hospitals NHS Trust Recruiting
Wolverhampton, West Midlands, United Kingdom, WV10 0QP
Contact: Matthew J Brookes, MRCP PhD       m.j.brookes@bham.ac.uk   
Contact: Hari Padmanabhan, MRCP       hari.padmanabhan@nhs.net   
University Hospitals Bristol Foundation NHS Turst Not yet recruiting
Bristol, United Kingdom, BS2 8HW
Contact: Robert Longman         
Principal Investigator: Robert Longman         
Derby Hospital NHS Foundation Trust Recruiting
Derby, United Kingdom, DE22 3NE
Contact: Jonathan Lund       jon.lund@nottingham.ac.uk   
Contact: Elena Theophilidou       etheophilidou@nhs.net   
Principal Investigator: Jonathan Lund         
St James University Hospitals NHS Trust Not yet recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Danilo Misckovic         
Principal Investigator: Danilo Miskovic         
University Hospitals of Leicester NHS Trust Not yet recruiting
Leicester, United Kingdom, LE1 5WW
Contact: Baljit Singh         
Principal Investigator: Baljit Singh         
Nottingham University Hospitals NHS Trust Recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Barrie D Keeler, MBBSBScMRCS    0115 8291145    barriekeeler@doctors.org.uk   
Contact: Austin G Acheson, MBBChMDFRCS    0115 8231147    austin.acheson@nottingham.ac.uk   
Principal Investigator: Barrie D Keeler, FRCS         
Yeovil District Hospital NHS Foundation Trust Recruiting
Yeovil, United Kingdom, BA21 4AT
Contact: Nader Francis       Nader.Francis@YDH.NHS.UK   
Contact: Joanna Allison       Joanna.Allison@YDH.NHS.UK   
Principal Investigator: Nader Francis         
Sponsors and Collaborators
Nottingham University Hospitals NHS Trust
National Institute for Health Research, United Kingdom
Investigators
Study Chair: Austin G Acheson, MBBS MD FRCS Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery
  More Information

No publications provided

Responsible Party: Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01701310     History of Changes
Other Study ID Numbers: 11GS005, 2011-002185-21, PB-PG-0110-21041
Study First Received: March 21, 2012
Last Updated: August 19, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Nottingham University Hospitals NHS Trust:
Adenocarcinoma
Anemia
Blood Transfusion
Colorectal surgery
Preoperative care
Perioperative care
Postoperative care
Iron
Hematinics
Hepcidin
Quality of life
Postoperative complications

Additional relevant MeSH terms:
Anemia
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Hematologic Diseases
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Ferric Compounds
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014