<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/NCT04464850</url>
  </required_header>
  <id_info>
    <org_study_id>MED-2563-07092</org_study_id>
    <nct_id>NCT04464850</nct_id>
  </id_info>
  <brief_title>Intravenous Versus Oral Iron Therapy in Hemodialysis Patients</brief_title>
  <acronym>IVO-IRON</acronym>
  <official_title>Effects Intravenous Iron and Oral Iron Therapy on Erythropoietin Dose in Maintenance Hemodialysis Patients: An Open-label, Randomized, Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiang Mai University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chiang Mai University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is aim to compare the efficacy of intravenous versus oral iron therapy regarding&#xD;
      the hemoglobin levels, iron status and erythropoietin dosage in maintenance hemodialysis&#xD;
      patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Run-in phase: All eligible patients will enter run-in phase for 2 weeks. In this phase, all&#xD;
      oral therapy that patients received before enrolment into the study will be discontinued.&#xD;
&#xD;
      Masking: Opened label&#xD;
&#xD;
      Allocation: Block of four randomization into 2 treatment arms: intravenous iron and oral iron&#xD;
&#xD;
      Safety criteria: Study participants who meet the following criteria will be discontinued from&#xD;
      the study. All patients data will be analyzed according to intention-to-treat principles.&#xD;
&#xD;
        -  Hemoglobin levels &lt; 6.0 g/dl&#xD;
&#xD;
        -  Packed red cells transfusion is required&#xD;
&#xD;
        -  Serum ferritin &gt;1,000 md/dl&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 29, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2021</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Maintenance hemodialysis patients who are eligible to enrol into the study according to inclusion and exclusion criteria will be start with 2-week run-in period before randomization. During this run-in period, all iron supplements that patients receive including oral and intravenous iron will be discontinued.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of epoetin dose</measure>
    <time_frame>24 weeks after randomization</time_frame>
    <description>Hemoglobin levels will be monitored and epoetin dose will be adjusted according to hemoglobin levels at 4, 12, 24 weeks after randomization.&#xD;
Protocols for epoetin dose adjustments are shown as follow. Hemoglobin levels (g/dl) Epoetin dose adjustment &lt;9.0 Increased by 50% 9.0 to &lt;10.0 Increased by 25% 10.0 to &lt;11.5 No change 11.5 to &lt;12.5 Decreased by 25%&#xD;
12.5 Decreased by 50%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin levels</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>Levels of hemoglobin concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythropoietin resistance index</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>Erythropoietin resistance index is calculated as the mean weekly epoetin dose per kg body weight divided by the average hemoglobin level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major cardiovascular events (MACE)</measure>
    <time_frame>24-week period after randomization</time_frame>
    <description>Major adverse cardiovascular events (MACE) is defined as a composite of nonfatal stroke, Nonfatal myocardial infarction, and cardiovascular death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unscheduled hospitalization</measure>
    <time_frame>24-week period after randomization</time_frame>
    <description>Numbers of any hospitalizations that is not planned</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization due to infections</measure>
    <time_frame>24-week period after randomization</time_frame>
    <description>Numbers of any hospitalizations that is caused by infections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein (CRP)</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>Serum levels of high sensitivity c-reactive protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The kidney disease quality of life (KDQOL) instrument</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>Quality of life will be assessed by the kidney disease quality of life (KDQOL) instrument</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life will be assessed by EQ-5D-5L (EuroQol - 5 Dimensions - 5 Levels)</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>EQ-5D-5L is the instrument used to evaluate health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain &amp; discomfort, Anxiety &amp; depression), each of which has five severity levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness of iron therapy</measure>
    <time_frame>4, 12, 24 weeks after randomization</time_frame>
    <description>The cost of iron therapy compared with the cost of epoetin</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">124</enrollment>
  <condition>Hemodialysis Complication</condition>
  <condition>Anemia</condition>
  <condition>Iron Deficiency Anemia</condition>
  <arm_group>
    <arm_group_label>Intravenous iron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Iron sucrose 200 mg every 2 weeks Folic acid 5 mg/day B6 10 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral iron</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ferrous fumarate 600 mg/day Folic acid 6.5 mg/day B6 15 mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous iron</intervention_name>
    <description>Iron sucrose will be given by continuous infusion for 1 hour during the last 1 hour of dialysis session. Iron sucrose will be given for 24 weeks during study period.&#xD;
Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization.&#xD;
The dosage of intravenous iron will be adjusted according to serum ferritin levels as follows.&#xD;
Serum ferritin &lt;500 mg/dl: iron sucrose 100 mg every 2 weeks Serum ferritin 500-800 mg/dl: iron sucrose 100 mg every 4 weeks Serum ferritin &gt;800 mg/dl: discontinue iron sucrose</description>
    <arm_group_label>Intravenous iron</arm_group_label>
    <other_name>Venofer, Encifer</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral iron</intervention_name>
    <description>1 tablet, three times a day, of iron fumarate will be prescribed for 24 weeks of study period.&#xD;
The dosage of iron fumarate will be adjusted according to serum ferritin levels as follows.&#xD;
Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization.&#xD;
Serum ferritin &lt;500 mg/dl: iron fumarate 200 mg three times daily Serum ferritin 500-800 mg/dl: iron fumarate 200 mg once daily Serum ferritin &gt;800 mg/dl: discontinue iron fumarate</description>
    <arm_group_label>Oral iron</arm_group_label>
    <other_name>Ferli-6 (ferrous fumarate 200 mg, folic acid 0.5 mg, B6 5 mg)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Hemodialysis for at least 3 months&#xD;
&#xD;
          -  Hemoglobin levels between 8 and 11.5 g/dl inclusive&#xD;
&#xD;
          -  Transferrin saturation (TSAT) &lt;50% and ferritin &lt;800 mg/dl&#xD;
&#xD;
          -  Stable dose of epoetin of any types and iron therapy for at least 1 month&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of iron allergy&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Patients with known hematologic disorders other than anemia of renal disease and iron&#xD;
             deficiency anemia&#xD;
&#xD;
          -  Patients with hemoglobinopathy e.g., thalassemia&#xD;
&#xD;
          -  Patients with iron overload or hemochromatosis&#xD;
&#xD;
          -  Patients with gastrointestinal hemorrhage during 6 months before enrolment in to the&#xD;
             study&#xD;
&#xD;
          -  Patients with current severe infection&#xD;
&#xD;
          -  Patients with any malignancies&#xD;
&#xD;
          -  Patients with severe psychiatric illness&#xD;
&#xD;
          -  Patients with any other medical condition which, in the Investigator's judgment, may&#xD;
             be associated with increased risk to the subject or may interfere with study&#xD;
             assessments or outcomes&#xD;
&#xD;
          -  Patients who currently receive medications that can altered gastrointestinal&#xD;
             absorption of oral iron e.g., aluminum carbonate, aluminum hydroxide, chloramphenicol,&#xD;
             dimercaprol&#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>Kajohnsak Noppakun, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instructor, Division of Nephrology, Department of Internal Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kajohnsak Noppakun, MD</last_name>
    <phone>+66815953465</phone>
    <email>kajohnsak.noppakun@cmu.ac.th</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tiranun Suriya, RN</last_name>
    <phone>+66818812106</phone>
    <email>tingsuri@hotmail.co.th</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kajohnsak Noppakun, MD</last_name>
      <phone>+66815953465</phone>
      <email>kajohnsak.noppakun@cmu.ac.th</email>
    </contact>
    <contact_backup>
      <last_name>Tiranun Suriya, RN</last_name>
      <phone>+66818812106</phone>
      <email>tingsuri@hotmail.co.th</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>August 7, 2020</last_update_submitted>
  <last_update_submitted_qc>August 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chiang Mai University</investigator_affiliation>
    <investigator_full_name>Kajohnsak Noppakun</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Iron therapy</keyword>
  <keyword>Hemodialysis</keyword>
  <keyword>Iron status</keyword>
  <keyword>Epoetin dose</keyword>
  <keyword>Intravenous iron</keyword>
  <keyword>Oral iron</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron</mesh_term>
    <mesh_term>Ferrous fumarate</mesh_term>
    <mesh_term>Folic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Request for individual participant data (IPD) has to be submitted to the Institutional Review Board (IRB) of Faculty of Medicine, Chiang Mai University, Chiang Mai, THAILAND.</ipd_description>
  </patient_data>
  <!-- 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/NCT04464850
org study id: MED-2563-07092
nct id: NCT04464850
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is aim to compare the efficacy of intravenous versus oral iron therapy regarding
      the hemoglobin levels, iron status and erythropoietin dosage in maintenance hemodialysis
      patients
Run-in phase: All eligible patients will enter run-in phase for 2 weeks. In this phase, all
      oral therapy that patients received before enrolment into the study will be discontinued.

      Masking: Opened label

      Allocation: Block of four randomization into 2 treatment arms: intravenous iron and oral iron

      Safety criteria: Study participants who meet the following criteria will be discontinued from
      the study. All patients data will be analyzed according to intention-to-treat principles.

        -  Hemoglobin levels < 6.0 g/dl

        -  Packed red cells transfusion is required

        -  Serum ferritin >1,000 md/dl
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Maintenance hemodialysis patients who are eligible to enrol into the study according to inclusion and exclusion criteria will be start with 2-week run-in period before randomization. During this run-in period, all iron supplements that patients receive including oral and intravenous iron will be discontinued.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Changes of epoetin dose
time frame: 24 weeks after randomization
description: Hemoglobin levels will be monitored and epoetin dose will be adjusted according to hemoglobin levels at 4, 12, 24 weeks after randomization.
Protocols for epoetin dose adjustments are shown as follow. Hemoglobin levels (g/dl) Epoetin dose adjustment <9.0 Increased by 50% 9.0 to <10.0 Increased by 25% 10.0 to <11.5 No change 11.5 to <12.5 Decreased by 25%
12.5 Decreased by 50%
measure: Hemoglobin levels
time frame: 4, 12, 24 weeks after randomization
description: Levels of hemoglobin concentration
measure: Erythropoietin resistance index
time frame: 4, 12, 24 weeks after randomization
description: Erythropoietin resistance index is calculated as the mean weekly epoetin dose per kg body weight divided by the average hemoglobin level
measure: Major cardiovascular events (MACE)
time frame: 24-week period after randomization
description: Major adverse cardiovascular events (MACE) is defined as a composite of nonfatal stroke, Nonfatal myocardial infarction, and cardiovascular death
measure: Unscheduled hospitalization
time frame: 24-week period after randomization
description: Numbers of any hospitalizations that is not planned
measure: Hospitalization due to infections
time frame: 24-week period after randomization
description: Numbers of any hospitalizations that is caused by infections
measure: C-reactive protein (CRP)
time frame: 4, 12, 24 weeks after randomization
description: Serum levels of high sensitivity c-reactive protein
measure: The kidney disease quality of life (KDQOL) instrument
time frame: 4, 12, 24 weeks after randomization
description: Quality of life will be assessed by the kidney disease quality of life (KDQOL) instrument
measure: Quality of life will be assessed by EQ-5D-5L (EuroQol - 5 Dimensions - 5 Levels)
time frame: 4, 12, 24 weeks after randomization
description: EQ-5D-5L is the instrument used to evaluate health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain & discomfort, Anxiety & depression), each of which has five severity levels
measure: Cost-effectiveness of iron therapy
time frame: 4, 12, 24 weeks after randomization
description: The cost of iron therapy compared with the cost of epoetin
arm group label: Intravenous iron
arm group type: Experimental
description: Iron sucrose 200 mg every 2 weeks Folic acid 5 mg/day B6 10 mg/day
arm group label: Oral iron
arm group type: Active Comparator
description: Ferrous fumarate 600 mg/day Folic acid 6.5 mg/day B6 15 mg/day
intervention type: Drug
intervention name: Intravenous iron
description: Iron sucrose will be given by continuous infusion for 1 hour during the last 1 hour of dialysis session. Iron sucrose will be given for 24 weeks during study period.
Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization.
The dosage of intravenous iron will be adjusted according to serum ferritin levels as follows.
Serum ferritin <500 mg/dl: iron sucrose 100 mg every 2 weeks Serum ferritin 500-800 mg/dl: iron sucrose 100 mg every 4 weeks Serum ferritin >800 mg/dl: discontinue iron sucrose
arm group label: Intravenous iron
other name: Venofer, Encifer
intervention type: Drug
intervention name: Oral iron
description: 1 tablet, three times a day, of iron fumarate will be prescribed for 24 weeks of study period.
The dosage of iron fumarate will be adjusted according to serum ferritin levels as follows.
Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization.
Serum ferritin <500 mg/dl: iron fumarate 200 mg three times daily Serum ferritin 500-800 mg/dl: iron fumarate 200 mg once daily Serum ferritin >800 mg/dl: discontinue iron fumarate
arm group label: Oral iron
other name: Ferli-6 (ferrous fumarate 200 mg, folic acid 0.5 mg, B6 5 mg)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kajohnsak Noppakun, MD
role: Principal Investigator
affiliation: Instructor, Division of Nephrology, Department of Internal Medicine
last name: Kajohnsak Noppakun, MD
phone: +66815953465
email: kajohnsak.noppakun@cmu.ac.th
last name: Tiranun Suriya, RN
phone: +66818812106
email: tingsuri@hotmail.co.th
facility: 
status: Recruiting
contact: 
contact backup: 
country: Thailand
responsible party type: Principal Investigator
investigator affiliation: Chiang Mai University
investigator full name: Kajohnsak Noppakun
investigator title: Assistant Professor of Medicine
mesh term: Anemia
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
mesh term: Iron
mesh term: Ferrous fumarate
mesh term: Folic Acid
sharing ipd: No
ipd description: Request for individual participant data (IPD) has to be submitted to the Institutional Review Board (IRB) of Faculty of Medicine, Chiang Mai University, Chiang Mai, THAILAND.