<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/NCT02198508</url>
  </required_header>
  <id_info>
    <org_study_id>DMR-096-IRB-037</org_study_id>
    <nct_id>NCT02198508</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Deferasirox Combination Treatment With Deferiprone In Thalassaemia Patients</brief_title>
  <official_title>The Shuttle Effect : Combination Therapy With Deferiprone and Deferasirox in Transfusion-dependent Thalassemia Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Medical University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Three iron chelators now available on the market differ in toxicity and organ&#xD;
      specificity; evidence on standardized chelation protocol remains inconclusive, but patients&#xD;
      with transfusion-dependent beta-thalassemia treated with DFO infusion show significant&#xD;
      differences in the limitations of daily activities, physical activity, and quality of life&#xD;
      when treated with oral chelator. With licensing of DFP in America, it is reasonable to&#xD;
      combine DFP with DFX. Patients find two oral chelators more acceptable than one oral and one&#xD;
      injectable. This pilot study rates use of DFP for improving iron excretion profile of&#xD;
      deferasirox.&#xD;
&#xD;
      Methods: The investigators enrolled 13 beta-thalassemia patients in China Medical University&#xD;
      Children's Hospital in May 2009-October 2011. Five refused to take part in pharmacokinetics;&#xD;
      they only participated in iron excretion study. Seven with irregular bowel function were&#xD;
      unable to collect feces in the screening period as baseline data. Subjects were randomly&#xD;
      assigned and rotated to undergo all treatments (with informed consent): (A) single oral dose&#xD;
      of DFX 30 mg/kg once daily, (B) single oral dose of DFP 40 mg/kg twice a day, (C) oral doses&#xD;
      of DFX and DFP administered sequentially (DFX 30 mg/kg/d, deferiprone 40 mg/kg/d and&#xD;
      deferiprone 40 mg/kg/d at 7-hour intervals). Three-day drug dosage was followed by four-day&#xD;
      washout. Collections of urine and stool proceeded 24 hours per day, each analyzed separately.&#xD;
      Through a venous catheter, serial blood samples (1 mL/each sampling) were collected in glass&#xD;
      tubes containing heparin as anticoagulant at Time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5,&#xD;
      3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dose; plasma concentrations of DFP and DFX&#xD;
      were measured.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2007</start_date>
  <primary_completion_date type="Actual">July 2008</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>iron excretion from urine and feces by flame atomic absorption spectroscopy</measure>
    <time_frame>25-days</time_frame>
    <description>Collections of urine and stool (made 24 hours a day) were analyzed separately.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>drug concentration in plasma by pharmacokinetics analysis</measure>
    <time_frame>25-day</time_frame>
    <description>Through a venous catheter, serial blood samples (1 mL/each sampling) were collected into glass tubes containing heparin as an anticoagulant at time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dosing. Blood samples were centrifuged, with plasma collected and frozen at -20°C until analysis.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Beta-thalassemia Major</condition>
  <arm_group>
    <arm_group_label>DFX single treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a single oral dose of DFX 30 mg/kg once daily, (Exjade®, Novartis Pharmaceuticals Corporation, USA )</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DFP single treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single oral dose of DFP 40 mg/kg/day twice a day, (Kelfer®, Cipla Ltd., India)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>combination treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>sequential oral doses of DFX 30 mg/kg/d, DFP 40 mg/kg/d and DFP 40 mg/kg/d (dosing interval: seven hours).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DFX(Deferasirox)</intervention_name>
    <arm_group_label>DFX single treatment</arm_group_label>
    <arm_group_label>combination treatment</arm_group_label>
    <other_name>Exjade®, Novartis Pharmaceuticals Corporation, USA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DFP(Deferiprone)</intervention_name>
    <arm_group_label>DFP single treatment</arm_group_label>
    <arm_group_label>combination treatment</arm_group_label>
    <other_name>Kelfer®, Cipla Ltd., India</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  serum ferritin greater than 2000 ng/mL,&#xD;
&#xD;
          -  serum creatinine within normal range for a measuring laboratory&#xD;
&#xD;
          -  platelet count exceeding 140000/mm3&#xD;
&#xD;
          -  body weight at least 40 Kg&#xD;
&#xD;
          -  None had a history of clinical significant of gastrointestinal, hepatic, renal,&#xD;
             endocrine, oncologic, infectious, pulmonary or cardiovascular disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV positive, history of immunologic hypersensitivity to any medication&#xD;
&#xD;
          -  women pregnant or breast feeding&#xD;
&#xD;
          -  drug or alcohol abuse&#xD;
&#xD;
          -  patients showed abnormal or irregular bowel function (defined as more than three bowel&#xD;
             movements a day or less than one bowel movement every other day)&#xD;
&#xD;
          -  receiving warfarin, digoxin, or anti-arrhythmic or antiseizure medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>July 22, 2014</last_update_submitted>
  <last_update_submitted_qc>July 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 23, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>China Medical University, Taiwan</investigator_affiliation>
    <investigator_full_name>Ching-Tien Peng</investigator_full_name>
    <investigator_title>superintendent</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deferasirox</mesh_term>
    <mesh_term>Deferiprone</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 28, 2015</submitted>
    <returned>August 21, 2015</returned>
  </pending_results>
  <!-- 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/NCT02198508
org study id: DMR-096-IRB-037
nct id: NCT02198508
lead sponsor: 
has dmc: Yes
Background: Three iron chelators now available on the market differ in toxicity and organ
      specificity; evidence on standardized chelation protocol remains inconclusive, but patients
      with transfusion-dependent beta-thalassemia treated with DFO infusion show significant
      differences in the limitations of daily activities, physical activity, and quality of life
      when treated with oral chelator. With licensing of DFP in America, it is reasonable to
      combine DFP with DFX. Patients find two oral chelators more acceptable than one oral and one
      injectable. This pilot study rates use of DFP for improving iron excretion profile of
      deferasirox.

      Methods: The investigators enrolled 13 beta-thalassemia patients in China Medical University
      Children's Hospital in May 2009-October 2011. Five refused to take part in pharmacokinetics;
      they only participated in iron excretion study. Seven with irregular bowel function were
      unable to collect feces in the screening period as baseline data. Subjects were randomly
      assigned and rotated to undergo all treatments (with informed consent): (A) single oral dose
      of DFX 30 mg/kg once daily, (B) single oral dose of DFP 40 mg/kg twice a day, (C) oral doses
      of DFX and DFP administered sequentially (DFX 30 mg/kg/d, deferiprone 40 mg/kg/d and
      deferiprone 40 mg/kg/d at 7-hour intervals). Three-day drug dosage was followed by four-day
      washout. Collections of urine and stool proceeded 24 hours per day, each analyzed separately.
      Through a venous catheter, serial blood samples (1 mL/each sampling) were collected in glass
      tubes containing heparin as anticoagulant at Time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5,
      3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dose; plasma concentrations of DFP and DFX
      were measured.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: iron excretion from urine and feces by flame atomic absorption spectroscopy
time frame: 25-days
description: Collections of urine and stool (made 24 hours a day) were analyzed separately.
measure: drug concentration in plasma by pharmacokinetics analysis
time frame: 25-day
description: Through a venous catheter, serial blood samples (1 mL/each sampling) were collected into glass tubes containing heparin as an anticoagulant at time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dosing. Blood samples were centrifuged, with plasma collected and frozen at -20°C until analysis.
arm group label: DFX single treatment
arm group type: Active Comparator
description: a single oral dose of DFX 30 mg/kg once daily, (Exjade®, Novartis Pharmaceuticals Corporation, USA )
arm group label: DFP single treatment
arm group type: Active Comparator
description: single oral dose of DFP 40 mg/kg/day twice a day, (Kelfer®, Cipla Ltd., India)
arm group label: combination treatment
arm group type: Experimental
description: sequential oral doses of DFX 30 mg/kg/d, DFP 40 mg/kg/d and DFP 40 mg/kg/d (dosing interval: seven hours).
intervention type: Drug
intervention name: DFX(Deferasirox)
arm group label: DFX single treatment
arm group label: combination treatment
other name: Exjade®, Novartis Pharmaceuticals Corporation, USA
intervention type: Drug
intervention name: DFP(Deferiprone)
arm group label: DFP single treatment
arm group label: combination treatment
other name: Kelfer®, Cipla Ltd., India
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: China Medical University, Taiwan
investigator full name: Ching-Tien Peng
investigator title: superintendent
mesh term: Thalassemia
mesh term: beta-Thalassemia
mesh term: Deferasirox
mesh term: Deferiprone
submitted: July 28, 2015
returned: August 21, 2015