<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/NCT03777514</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00198735</org_study_id>
    <nct_id>NCT03777514</nct_id>
  </id_info>
  <brief_title>Intravenous (IV) Versus Oral Iron Treatment of Iron Deficiency Anemia in the Post-operative Bariatric Surgical Patient</brief_title>
  <official_title>A Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of Iron Deficiency Anemia in the Post-operative Bariatric Surgical Patient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to compare two accepted treatments for iron deficiency anemia (oral&#xD;
      ferrous sulfate and intravenous ferumoxytol) for efficacy and speed of response in the&#xD;
      treatment of iron deficiency anemia (IDA) in the post-operative bariatric surgical patient.&#xD;
      In this study, 104 bariatric surgical post-operative patients will be randomly assigned 52&#xD;
      each to oral or 52 to a single dose IV iron treatment using double-blind procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale for study: The preponderance of published evidence reports superior efficacy and&#xD;
      decreased toxicity of intravenous iron compared to oral iron in correcting anemia and iron&#xD;
      parameters in published trials of bariatric surgery patients. Intravenous, and not oral, iron&#xD;
      ensures adequate delivery and avoids gastrointestinal toxicities, which may be especially&#xD;
      burdensome in these patients who require optimal levels of energy to maintain prudent&#xD;
      exercise programs recommended by patients' bariatric practitioners. Uncontradicted published&#xD;
      evidence reports safety and efficacy of complete replacement doses of intravenous iron&#xD;
      administered in one or two doses of either low molecular weight iron dextran, ferumoxytol,&#xD;
      ferric carboxymaltose or iron isomaltoside. A common feature of all studies extant is the&#xD;
      lack of reported serious adverse events. Even in patients with minimally invasive procedures&#xD;
      such as gastric banding or stapling in whom oral iron may be tolerated, given the often&#xD;
      present multiple gastrointestinal perturbations, intravenous iron may simplify care.&#xD;
&#xD;
      Drugs used: The investigators propose to use and FDA approved IV iron preparation -&#xD;
      ferumoxytol, administered as two doses (over a interval of 2 to 7 days), each 510 mg over&#xD;
      fifteen minutes based on published prospective safety and efficacy data and compare the&#xD;
      effectiveness of the treatment to the American Metabolic and Bariatric Associations&#xD;
      recommended treatment for iron deficiency anemia in the post-operative bariatric patients of&#xD;
      oral iron ferrous sulphate 325 mg twice daily for 6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study wasn't started.&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 2019</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2021</primary_completion_date>
  <phase>N/A</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>The study is a randomized, comparative double blind, double dummy study to evaluate efficacy and time course of treatment response of bariatric surgical patients found to have IDA, three months or greater following bariatric surgery (Roux-en Y gastric bypass and vertical sleeve gastrectomy) over 6 weeks with a 46-week follow-up extension. Two medications and placebos will be used with equal random assignment to both groups&#xD;
Ferumoxytol intravenous (IV) 1020 mg as - 2 vials of 510 mg (510 mg IV over 15 minutes) each given 2-7 days apart.&#xD;
Ferrous sulfate 325 mg (oral) tabs morning and evening.&#xD;
Placebo: oral vitamin C 500 mg tabs, saline infusion</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The IV bags will be opaque and patients will be asked to wear a eye mask during the infusion of iron vs. saline.&#xD;
The oral tables will be identical in color and shape (iron in the form of ferrous sulphate and vitamin C)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Resolution of anemia in oral vs. IV iron as assessed by Clinical Global Impression (CGI) - 2 score</measure>
    <time_frame>6 weeks</time_frame>
    <description>The CGI-2 is a one-item questionnaire which asks how participants feel now compared to before receiving treatment. It has a scoring of 1 to 7 with 1 meaning much better and 7 meaning very much worse</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Resolution of anemia in oral vs. IV iron as assessed by ferritin level</measure>
    <time_frame>6 weeks</time_frame>
    <description>Participants will be assessed after six weeks to see if there is a resolution of anemia following the treatment with oral or IV iron. This will be determined by the ferritin level. Ferritin &gt; 20% will be the cutoff for resolution of anemia.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Resolution of anemia in oral vs. IV iron as assessed by TSAT</measure>
    <time_frame>6 weeks</time_frame>
    <description>Participants will be assessed after six weeks to see if there is a resolution of anemia following the treatment with oral or IV iron. This will be determined by TSAT level. TSAT &gt; 19% will be the cutoff for resolution of anemia.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time (weeks) to treatment response as assessed by CGI-2 score</measure>
    <time_frame>6 weeks</time_frame>
    <description>The CGI-2 is a one-item questionnaire which asks how participants feel now compared to before receiving treatment. It has a scoring of 1 to 7 with 1 meaning much better and 7 meaning very much worse. This will be used in assessing the time in weeks when participant noticed a change after receiving treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time (weeks) to treatment response as assessed by ferritin level</measure>
    <time_frame>6 weeks</time_frame>
    <description>Participants will be assessed after six weeks to identify what time (in weeks) ferritin level was &gt; 20% following the treatment with oral or IV iron</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time (weeks) to treatment response as assessed by TSAT</measure>
    <time_frame>6 weeks</time_frame>
    <description>Participants will be assessed after six weeks to identify what time (in weeks) TSAT level was &gt; 19% following the treatment with oral or IV iron</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Need for continued treatment as assessed by ferritin level</measure>
    <time_frame>1 year</time_frame>
    <description>Participants will be assessed after a year to see if participants require continued treatment following the treatment with oral or IV iron. This will be determined by the ferritin level. Ferritin &gt; 20% will be the cutoff for no further need for treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for continued treatment as assessed by TSAT</measure>
    <time_frame>1 year</time_frame>
    <description>Participants will be assessed after a year to see if participants require continued treatment following the treatment with oral or IV iron. This will be determined by TSAT level. TSAT &gt; 19% will be the cutoff for no further need for treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>IDA in the Post-bariatric Surgical Patient</condition>
  <arm_group>
    <arm_group_label>IV iron</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ferumoxytol intravenous (IV) 1020 mg as - 2 vials of 510 mg (510 mg IV over 15 minutes) each given 2-7 days apart.&#xD;
Participants in this group will also receive oral vitamin C as a placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oral iron</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ferrous sulfate 325 mg (oral) tabs morning and evening. Participants in this group will also receive intravenous normal saline as a placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferumoxytol</intervention_name>
    <description>treatment of iron deficiency anemia with IV iron.</description>
    <arm_group_label>IV iron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferrous sulfate</intervention_name>
    <description>treatment of iron deficiency anemia with oral iron</description>
    <arm_group_label>oral iron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral vitamin C</intervention_name>
    <description>Oral vitamin C to be used as a placebo for participants receiving IV iron</description>
    <arm_group_label>IV iron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intravenous normal saline</intervention_name>
    <description>Intravenous normal saline will be used as placebo for participants receiving oral iron</description>
    <arm_group_label>oral iron</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged ≥ 18 years&#xD;
&#xD;
          -  Patients who have undergone a Roux-en Y Gastric Bypass or Vertical Sleeve Gastrectomy&#xD;
             and are at least 3 months or more out from surgery.&#xD;
&#xD;
          -  Iron deficiency anemia defined as iron deficient with either ferritin &lt; 20 mcg/l,&#xD;
             transferrin saturation (TSAT) &lt; 19%, or anemia with Hgb &lt; 13 g/dL for both males and&#xD;
             females.&#xD;
&#xD;
          -  Willingness to use contraceptive to avoid pregnancy: Women have to be surgically&#xD;
             sterile, post menopausal or use one of the following contraceptives during the whole&#xD;
             study period and after the study has ended for at least five times the plasma&#xD;
             biological half-life of the investigational medicinal product: intrauterine devices or&#xD;
             hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal&#xD;
             vaginal devices, or injections with prolonged release).&#xD;
&#xD;
          -  Willingness to participate and signing the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Iron overload or disturbances in utilization of iron (e.g. hemochromatosis and&#xD;
             hemosiderosis)&#xD;
&#xD;
          -  Decompensated liver cirrhosis or active hepatitis (ALT &gt; 3 times upper limit of&#xD;
             normal)&#xD;
&#xD;
          -  Serum ferritin &gt; 500 ng/mL or transferrin saturation &gt; 40%&#xD;
&#xD;
          -  Active acute or chronic infections (assessed by clinical judgment that may be&#xD;
             indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are&#xD;
             available)&#xD;
&#xD;
          -  Rheumatoid arthritis with symptoms or signs of active inflammation&#xD;
&#xD;
          -  Pregnant and nursing women&#xD;
&#xD;
          -  History of multiple allergies&#xD;
&#xD;
          -  Known hypersensitivity to ferumoxytol or oral iron or any excipients in the drug&#xD;
             products&#xD;
&#xD;
          -  Previous IV iron treatment for IDA&#xD;
&#xD;
          -  Other iron treatment or blood transfusion within 4 weeks prior to the screening or&#xD;
             treatment visit&#xD;
&#xD;
          -  Planned elective surgery during the study&#xD;
&#xD;
          -  Any other medical condition that, in the opinion of Investigator, may cause the&#xD;
             subject to be unsuitable for the completion of the study or place the subject at&#xD;
             potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension,&#xD;
             unstable ischemic heart disease, or uncontrolled diabetes mellitus&#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>Kimberley E Steele, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>September 9, 2019</last_update_submitted>
  <last_update_submitted_qc>September 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Ferrosoferric Oxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03777514
org study id: IRB00198735
nct id: NCT03777514
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of the study is to compare two accepted treatments for iron deficiency anemia (oral
      ferrous sulfate and intravenous ferumoxytol) for efficacy and speed of response in the
      treatment of iron deficiency anemia (IDA) in the post-operative bariatric surgical patient.
      In this study, 104 bariatric surgical post-operative patients will be randomly assigned 52
      each to oral or 52 to a single dose IV iron treatment using double-blind procedures.
Rationale for study: The preponderance of published evidence reports superior efficacy and
      decreased toxicity of intravenous iron compared to oral iron in correcting anemia and iron
      parameters in published trials of bariatric surgery patients. Intravenous, and not oral, iron
      ensures adequate delivery and avoids gastrointestinal toxicities, which may be especially
      burdensome in these patients who require optimal levels of energy to maintain prudent
      exercise programs recommended by patients' bariatric practitioners. Uncontradicted published
      evidence reports safety and efficacy of complete replacement doses of intravenous iron
      administered in one or two doses of either low molecular weight iron dextran, ferumoxytol,
      ferric carboxymaltose or iron isomaltoside. A common feature of all studies extant is the
      lack of reported serious adverse events. Even in patients with minimally invasive procedures
      such as gastric banding or stapling in whom oral iron may be tolerated, given the often
      present multiple gastrointestinal perturbations, intravenous iron may simplify care.

      Drugs used: The investigators propose to use and FDA approved IV iron preparation -
      ferumoxytol, administered as two doses (over a interval of 2 to 7 days), each 510 mg over
      fifteen minutes based on published prospective safety and efficacy data and compare the
      effectiveness of the treatment to the American Metabolic and Bariatric Associations
      recommended treatment for iron deficiency anemia in the post-operative bariatric patients of
      oral iron ferrous sulphate 325 mg twice daily for 6 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is a randomized, comparative double blind, double dummy study to evaluate efficacy and time course of treatment response of bariatric surgical patients found to have IDA, three months or greater following bariatric surgery (Roux-en Y gastric bypass and vertical sleeve gastrectomy) over 6 weeks with a 46-week follow-up extension. Two medications and placebos will be used with equal random assignment to both groups
Ferumoxytol intravenous (IV) 1020 mg as - 2 vials of 510 mg (510 mg IV over 15 minutes) each given 2-7 days apart.
Ferrous sulfate 325 mg (oral) tabs morning and evening.
Placebo: oral vitamin C 500 mg tabs, saline infusion
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The IV bags will be opaque and patients will be asked to wear a eye mask during the infusion of iron vs. saline.
The oral tables will be identical in color and shape (iron in the form of ferrous sulphate and vitamin C)
measure: Resolution of anemia in oral vs. IV iron as assessed by Clinical Global Impression (CGI) - 2 score
time frame: 6 weeks
description: The CGI-2 is a one-item questionnaire which asks how participants feel now compared to before receiving treatment. It has a scoring of 1 to 7 with 1 meaning much better and 7 meaning very much worse
measure: Resolution of anemia in oral vs. IV iron as assessed by ferritin level
time frame: 6 weeks
description: Participants will be assessed after six weeks to see if there is a resolution of anemia following the treatment with oral or IV iron. This will be determined by the ferritin level. Ferritin > 20% will be the cutoff for resolution of anemia.
measure: Resolution of anemia in oral vs. IV iron as assessed by TSAT
time frame: 6 weeks
description: Participants will be assessed after six weeks to see if there is a resolution of anemia following the treatment with oral or IV iron. This will be determined by TSAT level. TSAT > 19% will be the cutoff for resolution of anemia.
measure: Time (weeks) to treatment response as assessed by CGI-2 score
time frame: 6 weeks
description: The CGI-2 is a one-item questionnaire which asks how participants feel now compared to before receiving treatment. It has a scoring of 1 to 7 with 1 meaning much better and 7 meaning very much worse. This will be used in assessing the time in weeks when participant noticed a change after receiving treatment.
measure: Time (weeks) to treatment response as assessed by ferritin level
time frame: 6 weeks
description: Participants will be assessed after six weeks to identify what time (in weeks) ferritin level was > 20% following the treatment with oral or IV iron
measure: Time (weeks) to treatment response as assessed by TSAT
time frame: 6 weeks
description: Participants will be assessed after six weeks to identify what time (in weeks) TSAT level was > 19% following the treatment with oral or IV iron
measure: Need for continued treatment as assessed by ferritin level
time frame: 1 year
description: Participants will be assessed after a year to see if participants require continued treatment following the treatment with oral or IV iron. This will be determined by the ferritin level. Ferritin > 20% will be the cutoff for no further need for treatment.
measure: Need for continued treatment as assessed by TSAT
time frame: 1 year
description: Participants will be assessed after a year to see if participants require continued treatment following the treatment with oral or IV iron. This will be determined by TSAT level. TSAT > 19% will be the cutoff for no further need for treatment.
arm group label: IV iron
arm group type: Active Comparator
description: Ferumoxytol intravenous (IV) 1020 mg as - 2 vials of 510 mg (510 mg IV over 15 minutes) each given 2-7 days apart.
Participants in this group will also receive oral vitamin C as a placebo.
arm group label: oral iron
arm group type: Active Comparator
description: Ferrous sulfate 325 mg (oral) tabs morning and evening. Participants in this group will also receive intravenous normal saline as a placebo.
intervention type: Drug
intervention name: Ferumoxytol
description: treatment of iron deficiency anemia with IV iron.
arm group label: IV iron
intervention type: Drug
intervention name: Ferrous sulfate
description: treatment of iron deficiency anemia with oral iron
arm group label: oral iron
intervention type: Other
intervention name: Oral vitamin C
description: Oral vitamin C to be used as a placebo for participants receiving IV iron
arm group label: IV iron
intervention type: Other
intervention name: Intravenous normal saline
description: Intravenous normal saline will be used as placebo for participants receiving oral iron
arm group label: oral iron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kimberley E Steele, MD, Ph.D
role: Principal Investigator
affiliation: Johns Hopkins University
responsible party type: Sponsor
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
mesh term: Ferrosoferric Oxide
sharing ipd: No