<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01701310</url>
  </required_header>
  <id_info>
    <org_study_id>11GS005</org_study_id>
    <secondary_id>2011-002185-21</secondary_id>
    <secondary_id>PB-PG-0110-21041</secondary_id>
    <nct_id>NCT01701310</nct_id>
  </id_info>
  <brief_title>IVICA: Intravenous Iron in Colorectal Cancer Associated Anaemia</brief_title>
  <acronym>IVICA</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nottingham University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nottingham University Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      116 eligible patients with confirmed non-metastatic colorectal adenocarcinoma and anemia will&#xD;
      be randomized to receive either oral ferrous sulphate (control) or intravenous ferric&#xD;
      carboxymaltose (intervention).&#xD;
&#xD;
      It is hypothesized that intravenous iron supplementation is more efficacious than oral iron&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who are anemic at the time of operation have been shown to have an increased&#xD;
      frequency of complications including wound infection and longer post-operative admissions.&#xD;
      Similarly, patients who are anemic at the time of their cancer operation are more likely to&#xD;
      require a blood transfusion which may increase the risk of recurrence of the cancer.&#xD;
&#xD;
      At present, oral iron is often used to treat anemia preoperatively in an attempt to minimize&#xD;
      the risk above. This drug is often poorly tolerated due to the side effect profile. Blood&#xD;
      transfusions can also be administered but expose the patient to other risks including&#xD;
      infection and transfusion associated reactions. In order to overcome these issues,&#xD;
      intravenous iron preparations have been developed and have improved in safety.&#xD;
&#xD;
      This is a multi-center, randomized, open label clinical trial, which looks to investigate the&#xD;
      efficacy of intravenous iron is in the treatment of preoperative anemia in colorectal&#xD;
      patients. Patients will be randomized to receive intravenous ferric carboxymaltose (treatment&#xD;
      group) or oral ferrous sulphate (control). The outcomes reviewed will include the amount and&#xD;
      frequency of blood transfusions received, changes in patient blood profiles, patient quality&#xD;
      of life scores, operative complications and hospital length of stay. The role of hepcidin as&#xD;
      a biomarker of treatment response will also be assessed.&#xD;
&#xD;
      The primary hypothesis to be tested is that intravenous iron will decrease transfusion rates.&#xD;
      To detect a significant clinical difference in blood transfused consistent with previous&#xD;
      published data (1 unit), 58 patients will be required in each arm of the study with 90% power&#xD;
      (alpha 0.05).&#xD;
&#xD;
      Randomization will be performed independently to the trial team using a computer generated&#xD;
      variable block randomization program.&#xD;
&#xD;
      All data will be confidentially recorded on a Case Report Form, as will drug reactions and&#xD;
      side effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <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</measure>
    <time_frame>0 - 6 to 12 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine differences in hemoglobin and hematinic markers between the groups.</measure>
    <time_frame>Enrollment to 6-12 weeks postoperatively</time_frame>
    <description>Hematinic markers include ferritin, iron, transferrin, transferrin saturation, erythropoietin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine differences in hepcidin levels in relation to blood profile changes in participants in the intravenous group.</measure>
    <time_frame>Enrollment to 6-12 weeks postoperatively.</time_frame>
    <description>To review the use of hepcidin as a biomarker to predict response to therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine differences in colonic mucosal expression of iron transport proteins, C-myc and NKD1 between the groups</measure>
    <time_frame>At point of operation only</time_frame>
    <description>Iron transport proteins include DMT TFR1, Ferroportin, Ferritin. As acquired from examination of pathology tissue specimen excised.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine differences in postoperative outcomes between the groups.</measure>
    <time_frame>Enrollment to 6-12 weeks postoperatively</time_frame>
    <description>Post-operative outcomes include morbidity, mortality, length of stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine differences in anemia symptomatology response between groups.</measure>
    <time_frame>Enrollment to 6-12 weeks postoperatively</time_frame>
    <description>Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Anemia</condition>
  <condition>Colorectal Neoplasm</condition>
  <arm_group>
    <arm_group_label>Ferric carboxymaltose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Ferrous Sulphate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferric carboxymaltose</intervention_name>
    <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.</description>
    <arm_group_label>Ferric carboxymaltose</arm_group_label>
    <other_name>Ferinject®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferrous Sulphate</intervention_name>
    <description>(Control) 200mg twice a day of oral ferrous sulphate will be administered for a minimum of a two week period</description>
    <arm_group_label>Ferrous Sulphate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosed with histologically proven colorectal adenocarcinoma.&#xD;
&#xD;
          -  Anemic at point of diagnosis of colorectal adenocarcinoma. (Haemoglobin values of &lt;12&#xD;
             g/dL for males and &lt;11 g/dL for females)&#xD;
&#xD;
          -  Medically fit for surgery.&#xD;
&#xD;
          -  Date of planned surgery is &gt;14 days from date of planned initiation of intervention&#xD;
             (intravenous ferric carboxymaltose /oral ferrous sulphate).&#xD;
&#xD;
          -  Able and willing to comply with all study requirements.&#xD;
&#xD;
          -  Willing to allow his/her General Practitioner and consultant, if appropriate, to be&#xD;
             notified of participation in the study.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Female participants who are pregnant, lactating or planning a pregnancy during the&#xD;
             course of the study.&#xD;
&#xD;
          -  Previous gastric, small bowel or colorectal surgery (where ≥50% of stomach or terminal&#xD;
             ileum has been resected)&#xD;
&#xD;
          -  Current chemotherapeutic treatment.&#xD;
&#xD;
          -  Known previous anaemia not attributable to colorectal carcinoma (i.e. anaemia in&#xD;
             patients with well established inflammatory disorders or chronic renal disease).&#xD;
&#xD;
          -  Known haematological disease.&#xD;
&#xD;
          -  Features necessitating urgent surgery (e.g. obstructive symptoms).&#xD;
&#xD;
          -  Previous allergy to intravenous iron or related iron products.&#xD;
&#xD;
          -  Significant symptomatic anemia necessitating urgent transfusion (e.g. cardiovascular&#xD;
             compromise)&#xD;
&#xD;
          -  Patients who are unable to consent.&#xD;
&#xD;
          -  Significant renal or hepatic impairment.&#xD;
&#xD;
          -  -Donation of blood during the study.&#xD;
&#xD;
          -  Participants who have participated in another research study involving an&#xD;
             investigational product in the past 12 weeks&#xD;
&#xD;
          -  Prisoners and minors (&lt;18 years)&#xD;
&#xD;
          -  Any other significant disease or disorder which, in the opinion of the Investigator,&#xD;
             may either put the participants at risk because of participation in the study, or may&#xD;
             influence the result of the study, or the participant's ability to participate in the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Austin G Acheson, MBBS MD FRCS</last_name>
    <role>Study Chair</role>
    <affiliation>Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Wolverhampton Hospitals NHS Trust</name>
      <address>
        <city>Wolverhampton</city>
        <state>West Midlands</state>
        <zip>WV10 0QP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol Foundation NHS Turst</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8HW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derby Hospital NHS Foundation Trust</name>
      <address>
        <city>Derby</city>
        <zip>DE22 3NE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James University Hospitals NHS Trust</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Leicester NHS Trust</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yeovil District Hospital NHS Foundation Trust</name>
      <address>
        <city>Yeovil</city>
        <zip>BA21 4AT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>March 21, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>October 27, 2016</last_update_submitted>
  <last_update_submitted_qc>October 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adenocarcinoma</keyword>
  <keyword>Anemia</keyword>
  <keyword>Blood Transfusion</keyword>
  <keyword>Colorectal surgery</keyword>
  <keyword>Preoperative care</keyword>
  <keyword>Perioperative care</keyword>
  <keyword>Postoperative care</keyword>
  <keyword>Iron</keyword>
  <keyword>Hematinics</keyword>
  <keyword>Hepcidin</keyword>
  <keyword>Quality of life</keyword>
  <keyword>Postoperative complications</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Anemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01701310
org study id: 11GS005
secondary id: 2011-002185-21
secondary id: PB-PG-0110-21041
nct id: NCT01701310
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
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
time frame: 0 - 6 to 12 weeks
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.
measure: To determine differences in hemoglobin and hematinic markers between the groups.
time frame: Enrollment to 6-12 weeks postoperatively
description: Hematinic markers include ferritin, iron, transferrin, transferrin saturation, erythropoietin.
measure: 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.
description: To review the use of hepcidin as a biomarker to predict response to therapy.
measure: 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
description: Iron transport proteins include DMT TFR1, Ferroportin, Ferritin. As acquired from examination of pathology tissue specimen excised.
measure: To determine differences in postoperative outcomes between the groups.
time frame: Enrollment to 6-12 weeks postoperatively
description: Post-operative outcomes include morbidity, mortality, length of stay.
measure: To determine differences in anemia symptomatology response between groups.
time frame: Enrollment to 6-12 weeks postoperatively
description: Quality of Life questionnaires will be used (SF-36[short form 36] and EQ-5D)
arm group label: Ferric carboxymaltose
arm group type: Experimental
arm group label: Ferrous Sulphate
arm group type: Active Comparator
intervention type: Drug
intervention name: Ferric carboxymaltose
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.
arm group label: Ferric carboxymaltose
other name: Ferinject®
intervention type: Drug
intervention name: Ferrous Sulphate
description: (Control) 200mg twice a day of oral ferrous sulphate will be administered for a minimum of a two week period
arm group label: Ferrous Sulphate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Austin G Acheson, MBBS MD FRCS
role: Study Chair
affiliation: Nottingham University Hospitals NHS Trust, Nottingham University, School of Clinical Sciences, Division of GI Surgery
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Anemia