<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/NCT02225886</url>
  </required_header>
  <id_info>
    <org_study_id>AWGRO 06/2014</org_study_id>
    <nct_id>NCT02225886</nct_id>
  </id_info>
  <brief_title>Ascorbic Acid Administration in the Treatment of Anemia in Chronic Hemodialysed Patients</brief_title>
  <acronym>FeVitC</acronym>
  <official_title>Effects of Ascorbic Acid Administration in the Treatment of Anemia in Chronic Hemodialysed Patients With Iron Overload</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anemia Working Group Romania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Anemia Working Group Romania</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The administration of ascorbic acid seemed to increase the iron available for erythropoiesis,&#xD;
      thus improving the anemia response to the treatment.&#xD;
&#xD;
      The investigators therefore aimed to evaluate the effects of intravenous ascorbic acid&#xD;
      administration in hemodialysed patients with iron overload.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Renal anemia is a complex condition in which chronic inflammation, among other factors, can&#xD;
      change the iron distribution by locking it in deposits, and also, iron metabolism parameters.&#xD;
      Thus, is hard to separate the iron functional deficit from overload.&#xD;
&#xD;
      The ascorbic acid is a hydrosoluble vitamin capable of reduction and hydrolysis. As a&#xD;
      reduction agent, the ascorbic acid supports the transformation of ferric iron to ferrous&#xD;
      iron. For instance, the ascorbic acid can increase digestive absorption and taking over the&#xD;
      iron without transferrin, helps iron release from ferritin and hemosiderin and delays&#xD;
      ferritin conversion to hemosiderin; therefore, the administration of ascorbic acid can&#xD;
      increase the quantity of iron available for erythropoiesis by realising it from the deposits.&#xD;
&#xD;
      Consequently, the antioxidant function of ascorbic acid can increase the red cells' lifetime,&#xD;
      reducing the inflammation and improving erythropoietin response Following these premises,&#xD;
      recent studies have examined the effect of administrating ascorbic acid to hemodialysed&#xD;
      patients with erythropoiesis stimulating agents (ESA) hyporesponsiveness anemia and&#xD;
      functional deficit or iron overload markers. The results of administering ascorbic acid&#xD;
      revealed an increased level of hemoglobin and transferrin saturation (TSAT) combined with the&#xD;
      decrease of ESA doses. The major limitations of these studies are the short amount of time&#xD;
      for observation (&lt;6months) and the limited number of participants which hampered neither the&#xD;
      complete evaluation of the goals, nor the adverse effects of supplementary administration of&#xD;
      vitamin C.&#xD;
&#xD;
      Until now, the Clinical practice guidelines of Kidney Disease do not recommend currently&#xD;
      using of high doses of vitamin C, considering the risk of a high level of oxalemia and the&#xD;
      limited information about the benefits. Considering this background, we intended to evaluate&#xD;
      the benefits of intravenous administration of ascorbic acid in hemodialysed patients with&#xD;
      iron balance markers suggestive for iron overload.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation of erythropoetin resistance index (ERI)</measure>
    <time_frame>12 months</time_frame>
    <description>Erythropoietin resistance index: the dose of ESA divided by the level of Hb - will be calculated monthly.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with Hb in the target range</measure>
    <time_frame>12 months</time_frame>
    <description>Percentage of patients with stable the hemoglobin in the target range (10.5-12g/dL), without any change in the weekly dose of ESA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ESA dose</measure>
    <time_frame>12 months</time_frame>
    <description>The number of reductions or increases in the ESA dose during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation in ESA dose</measure>
    <time_frame>12 months</time_frame>
    <description>The difference between the actual ESA dose and the one at baseline will be calculated monthly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of iron dose</measure>
    <time_frame>12 months</time_frame>
    <description>The difference between the actual iron dose and the one at baseline will be calculated monthly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with hemoglobin within target</measure>
    <time_frame>12 months</time_frame>
    <description>Percentage of patients with 10&lt;Hb&lt;12.1 g/dL will be calculated monthly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with target iron status</measure>
    <time_frame>12 months</time_frame>
    <description>Percentage of patients with 100&lt;serum ferritin&lt;800 ng/mL and 19&lt;transferrin saturation&lt;51% will be calculated monthly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of serum hepcidin</measure>
    <time_frame>12 months</time_frame>
    <description>Variation of serum hepcidin will be calculated every 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxalemia</measure>
    <time_frame>12 months</time_frame>
    <description>Serum oxalate level will be calculated every 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local and general tolerance to vitamin C</measure>
    <time_frame>12 months</time_frame>
    <description>Local and general tolerance to vitamin C will be evaluated monthly</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>Adverse events will be evaluated monthly</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of withdrawals and dropouts</measure>
    <time_frame>12 months</time_frame>
    <description>The number of withdrawals and dropouts will be calculated monthly</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Anaemia Response to the Treatment</condition>
  <condition>Peripheral Iron Indices</condition>
  <condition>Oxalemia</condition>
  <arm_group>
    <arm_group_label>Ascorbic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a 300 mg intravenous ascorbic acid, 3 times a week, postdialysis, except for the dialysis sessions when iv iron is administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive 100 mL saline solution, 3 times a week, with associated medication, except but the dialysis sessions when iv iron is administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ascorbic Acid</intervention_name>
    <description>300 mg of intravenous ascorbic acid will be given 3 times a week, postdialysis, in 100 mL saline solution, except for the dialysis sessions when iv iron is administered</description>
    <arm_group_label>Ascorbic acid</arm_group_label>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age above 18 years old&#xD;
&#xD;
          -  At least 6 months on hemodialysis at the time of randomization;&#xD;
&#xD;
          -  Kt/V≥1.2;&#xD;
&#xD;
          -  average of the last three serum ferritin levels &gt; 500 ng/mL AND&#xD;
&#xD;
          -  Average of the last three TSAT levels &gt; 20% and increasing&#xD;
&#xD;
          -  ERI in the 4th quartile of the group&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active bleeding or other cause of anemia&#xD;
&#xD;
          -  Serum level of intact parathyroid hormone (iPTH)&gt;800 pg/mL&#xD;
&#xD;
          -  Actual neoplasia&#xD;
&#xD;
          -  HIV, Hepatitis B or C infections&#xD;
&#xD;
          -  Significant inflammation (CRP&gt;12mg/L) or acute infection&#xD;
&#xD;
          -  Venous central catheter&#xD;
&#xD;
          -  Severe hepatic, cardiovascular, psychic disease or other severe comorbidities&#xD;
&#xD;
          -  Moderate or severe malnutrition&#xD;
&#xD;
          -  Blood transfusions in the 2 months prior to screening&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Inclusion in another clinical trial in the past month&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabriel Mircescu, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Anemia Working Group Romania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Liliana Garneata, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Anemia Workiing Group Romania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tudor Simionescu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>&quot;Carol Davila&quot; Teaching Hospital of Nephrology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Liliana Garneata, MD, PhD</last_name>
    <phone>+40722619358</phone>
    <email>liliana.garneata@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tudor Simionescu, MD PhD</last_name>
    <phone>+40732161766</phone>
    <email>tudorsimi@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>&quot;Nefrolab&quot; Dialysis Center</name>
      <address>
        <city>Slatina</city>
        <country>Romania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aurelian Simionescu, MD, PhD</last_name>
      <phone>+40732161768</phone>
      <email>relusimionescu@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Ileana Mihailescu, MD</last_name>
      <phone>+40730577485</phone>
      <email>dr_ilemih@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Romania</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 23, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>February 21, 2020</last_update_submitted>
  <last_update_submitted_qc>February 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Renal anaemia</keyword>
  <keyword>Intravenous ascorbic acid</keyword>
  <keyword>Intravenous iron administration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>24 months</ipd_time_frame>
  </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/NCT02225886
org study id: AWGRO 06/2014
nct id: NCT02225886
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The administration of ascorbic acid seemed to increase the iron available for erythropoiesis,
      thus improving the anemia response to the treatment.

      The investigators therefore aimed to evaluate the effects of intravenous ascorbic acid
      administration in hemodialysed patients with iron overload.
Renal anemia is a complex condition in which chronic inflammation, among other factors, can
      change the iron distribution by locking it in deposits, and also, iron metabolism parameters.
      Thus, is hard to separate the iron functional deficit from overload.

      The ascorbic acid is a hydrosoluble vitamin capable of reduction and hydrolysis. As a
      reduction agent, the ascorbic acid supports the transformation of ferric iron to ferrous
      iron. For instance, the ascorbic acid can increase digestive absorption and taking over the
      iron without transferrin, helps iron release from ferritin and hemosiderin and delays
      ferritin conversion to hemosiderin; therefore, the administration of ascorbic acid can
      increase the quantity of iron available for erythropoiesis by realising it from the deposits.

      Consequently, the antioxidant function of ascorbic acid can increase the red cells' lifetime,
      reducing the inflammation and improving erythropoietin response Following these premises,
      recent studies have examined the effect of administrating ascorbic acid to hemodialysed
      patients with erythropoiesis stimulating agents (ESA) hyporesponsiveness anemia and
      functional deficit or iron overload markers. The results of administering ascorbic acid
      revealed an increased level of hemoglobin and transferrin saturation (TSAT) combined with the
      decrease of ESA doses. The major limitations of these studies are the short amount of time
      for observation (<6months) and the limited number of participants which hampered neither the
      complete evaluation of the goals, nor the adverse effects of supplementary administration of
      vitamin C.

      Until now, the Clinical practice guidelines of Kidney Disease do not recommend currently
      using of high doses of vitamin C, considering the risk of a high level of oxalemia and the
      limited information about the benefits. Considering this background, we intended to evaluate
      the benefits of intravenous administration of ascorbic acid in hemodialysed patients with
      iron balance markers suggestive for iron overload.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Variation of erythropoetin resistance index (ERI)
time frame: 12 months
description: Erythropoietin resistance index: the dose of ESA divided by the level of Hb - will be calculated monthly.
measure: Percentage of patients with Hb in the target range
time frame: 12 months
description: Percentage of patients with stable the hemoglobin in the target range (10.5-12g/dL), without any change in the weekly dose of ESA
measure: Changes in ESA dose
time frame: 12 months
description: The number of reductions or increases in the ESA dose during the study
measure: Variation in ESA dose
time frame: 12 months
description: The difference between the actual ESA dose and the one at baseline will be calculated monthly.
measure: Variation of iron dose
time frame: 12 months
description: The difference between the actual iron dose and the one at baseline will be calculated monthly.
measure: Percentage of patients with hemoglobin within target
time frame: 12 months
description: Percentage of patients with 10<Hb<12.1 g/dL will be calculated monthly.
measure: Percentage of patients with target iron status
time frame: 12 months
description: Percentage of patients with 100<serum ferritin<800 ng/mL and 19<transferrin saturation<51% will be calculated monthly.
measure: Variation of serum hepcidin
time frame: 12 months
description: Variation of serum hepcidin will be calculated every 3 months
measure: Oxalemia
time frame: 12 months
description: Serum oxalate level will be calculated every 3 months
measure: Local and general tolerance to vitamin C
time frame: 12 months
description: Local and general tolerance to vitamin C will be evaluated monthly
measure: Adverse events
time frame: 12 months
description: Adverse events will be evaluated monthly
measure: The number of withdrawals and dropouts
time frame: 12 months
description: The number of withdrawals and dropouts will be calculated monthly
arm group label: Ascorbic acid
arm group type: Experimental
description: Patients will receive a 300 mg intravenous ascorbic acid, 3 times a week, postdialysis, except for the dialysis sessions when iv iron is administered.
arm group label: Control group
arm group type: Placebo Comparator
description: Patients will receive 100 mL saline solution, 3 times a week, with associated medication, except but the dialysis sessions when iv iron is administered.
intervention type: Drug
intervention name: Ascorbic Acid
description: 300 mg of intravenous ascorbic acid will be given 3 times a week, postdialysis, in 100 mL saline solution, except for the dialysis sessions when iv iron is administered
arm group label: Ascorbic acid
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Gabriel Mircescu, Professor
role: Study Chair
affiliation: Anemia Working Group Romania
last name: Liliana Garneata, MD, PhD
role: Study Director
affiliation: Anemia Workiing Group Romania
last name: Tudor Simionescu, MD, PhD
role: Principal Investigator
affiliation: "Carol Davila" Teaching Hospital of Nephrology
last name: Liliana Garneata, MD, PhD
phone: +40722619358
email: liliana.garneata@gmail.com
last name: Tudor Simionescu, MD PhD
phone: +40732161766
email: tudorsimi@yahoo.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Romania
responsible party type: Sponsor
mesh term: Anemia
mesh term: Ascorbic Acid
sharing ipd: Yes
ipd description: Publication
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: 24 months