<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/NCT03229746</url>
  </required_header>
  <id_info>
    <org_study_id>17200058</org_study_id>
    <nct_id>NCT03229746</nct_id>
  </id_info>
  <brief_title>Reposition of Second Line Treatment in Chronic Immune Thrombocytopenia</brief_title>
  <official_title>Reposition of Second Line Treatment in Chronic Immune Thrombocytopenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut 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>
      Hydroxychloroquine has been reported to have a clinically significant effect on the platelet&#xD;
      count in systemic lupus thrombocytopenia. Its action may be due to its immune modulator&#xD;
      effect. Immune thrombocytopenia (ITP) is known as an immune-mediated acquired disease&#xD;
      characterized by transient or persistent decrease of the platelet count. However, refractory&#xD;
      ITP is lacking of effective treatments and the efficacy of decitabine in ITP remains poorly&#xD;
      understood. Data from this study may provide some idea of Hydroxychloroquine in the treatment&#xD;
      of ITP in comparison to other lines of treatment as detected by the standardized definitions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will include patients with chronic ITP attending the out patients clinic of&#xD;
      Clinical Hematology Unit of Internal Medicine Department of Assiut university Hospital to&#xD;
      evaluate the safety and efficacy of hydroxychloroquine in comparison to other lines of&#xD;
      treatment as detected by the standardized definitions . Detect the predictors for chronic ITP&#xD;
      especially anti-nuclear antibodies (ANA) role and the effect of the proposed drugs on the&#xD;
      level of anti-platelet antibodies. Evaluation of the health-related quality of life after&#xD;
      treatments to answer this question; Is the most effective drug is linked to the best quality&#xD;
      of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">June 1, 2018</completion_date>
  <primary_completion_date type="Actual">June 1, 2018</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>Platelet count</measure>
    <time_frame>Follow up untill response or death from any cause up to six months</time_frame>
    <description>to detect response as the standard definition</description>
  </primary_outcome>
  <primary_outcome>
    <measure>side effects</measure>
    <time_frame>Up to six months</time_frame>
    <description>any complication for any line of treatments line</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>anti- nuclear antibodies role</measure>
    <time_frame>before enrollment</time_frame>
    <description>Detecting the predictors for chronic ITP especially ANA role</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-platelets antibodies role</measure>
    <time_frame>after6 months</time_frame>
    <description>Evaluation of the effect of the proposed drugs on the level of anti-platelet antibodies .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health quality life</measure>
    <time_frame>after 6 months of treatment</time_frame>
    <description>The Arabic version of the 36-Item Short Form Survey Instrument (SF-36) questionnaire will be administered to all patients before &amp; after treatment.&#xD;
This questionnaire is a validated one which assesses general health functioning .</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>hydroxychloroquine group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>hydroxychloroquine tablets 200mg ,two times/day for at least 6 month</description>
  </arm_group>
  <arm_group>
    <arm_group_label>vincristine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>vincristine ampoule , 1mg/ week, I.v drep over 2 hours for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>azathioprine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>azathioprine tablet 50mg, dose 100-150 mg daily for 6 month</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>200mg twice daily orally for at least 12 weeks</description>
    <arm_group_label>hydroxychloroquine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vincristine</intervention_name>
    <description>1mg intravenous weekly for 4 weeks</description>
    <arm_group_label>vincristine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>azathioprine</intervention_name>
    <description>dose 100mg daily for at least 3 weeks</description>
    <arm_group_label>azathioprine group</arm_group_label>
    <other_name>imuran</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  We will recruit patients with primary chronic ITP patients with ITP lasting for more&#xD;
             than 12 months which is proved to be refractory to the standard first line treatment&#xD;
             or need to treatment(s) (including, but not limited to, low dose of corticosteroids)&#xD;
             to minimize the risk of clinically significant bleeding.&#xD;
&#xD;
          -  Subject or their guardian has signed and dated a written informed consent.&#xD;
&#xD;
          -  Subject experienced no toxicity or known contraindication to any line of treatments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy.&#xD;
&#xD;
          -  liver and kidney function impairment.&#xD;
&#xD;
          -  hepatitis c virus(HCV), human immunodeficiency virus (HIV), hepatitis B virus&#xD;
             infection.&#xD;
&#xD;
          -  patients with systemic lupus erythematosus and/or antiphospholipid syndrome&#xD;
&#xD;
          -  lymphoproliferative disorders.&#xD;
&#xD;
          -  an active malignancy&#xD;
&#xD;
          -  an arterial or venous thrombosis&#xD;
&#xD;
          -  Grade III-IV cardiovascular disease .&#xD;
&#xD;
          -  Recent history of alcohol/drug abuse.&#xD;
&#xD;
          -  Subjects recently treated with drugs that affect platelet function (including but not&#xD;
             limited to aspirin, clopidogrel and/or NSAIDs) or anti-coagulants for &gt; 3 consecutive&#xD;
             days within 2 weeks of the study start and until the end of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Assiut university hospital</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Park YH, Yi HG, Lee MH, Kim CS, Lim JH. Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study. Int J Hematol. 2016 Feb;103(2):180-8. doi: 10.1007/s12185-015-1903-0. Epub 2015 Nov 20.</citation>
    <PMID>26588926</PMID>
  </reference>
  <reference>
    <citation>Poudyal BS, Sapkota B, Shrestha GS, Thapalia S, Gyawali B, Tuladhar S. Safety and Efficacy of Azathioprine as a Second Line Therapy for Primary Immune Thrombocytopenic Purpura. JNMA J Nepal Med Assoc. 2016 Jul-Sep;55(203):16-21.</citation>
    <PMID>27935917</PMID>
  </reference>
  <reference>
    <citation>Cooper N. State of the art - how I manage immune thrombocytopenia. Br J Haematol. 2017 Apr;177(1):39-54. doi: 10.1111/bjh.14515. Epub 2017 Mar 10. Erratum In: Br J Haematol. 2017 May;177(4):661.</citation>
    <PMID>28295192</PMID>
  </reference>
  <reference>
    <citation>Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur J Haematol Suppl. 2009 Mar;(71):3-7. doi: 10.1111/j.1600-0609.2008.01206.x.</citation>
    <PMID>19200301</PMID>
  </reference>
  <results_reference>
    <citation>Khellaf M, Chabrol A, Mahevas M, Roudot-Thoraval F, Limal N, Languille L, Bierling P, Michel M, Godeau B. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies. Am J Hematol. 2014 Feb;89(2):194-8. doi: 10.1002/ajh.23609. Epub 2013 Nov 20.</citation>
    <PMID>24254965</PMID>
  </results_reference>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>July 23, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>June 27, 2018</last_update_submitted>
  <last_update_submitted_qc>June 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Ghada E. M. Abdallah</investigator_full_name>
    <investigator_title>Principal investegator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Azathioprine</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/NCT03229746
org study id: 17200058
nct id: NCT03229746
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Hydroxychloroquine has been reported to have a clinically significant effect on the platelet
      count in systemic lupus thrombocytopenia. Its action may be due to its immune modulator
      effect. Immune thrombocytopenia (ITP) is known as an immune-mediated acquired disease
      characterized by transient or persistent decrease of the platelet count. However, refractory
      ITP is lacking of effective treatments and the efficacy of decitabine in ITP remains poorly
      understood. Data from this study may provide some idea of Hydroxychloroquine in the treatment
      of ITP in comparison to other lines of treatment as detected by the standardized definitions.
This study will include patients with chronic ITP attending the out patients clinic of
      Clinical Hematology Unit of Internal Medicine Department of Assiut university Hospital to
      evaluate the safety and efficacy of hydroxychloroquine in comparison to other lines of
      treatment as detected by the standardized definitions . Detect the predictors for chronic ITP
      especially anti-nuclear antibodies (ANA) role and the effect of the proposed drugs on the
      level of anti-platelet antibodies. Evaluation of the health-related quality of life after
      treatments to answer this question; Is the most effective drug is linked to the best quality
      of life.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Platelet count
time frame: Follow up untill response or death from any cause up to six months
description: to detect response as the standard definition
measure: side effects
time frame: Up to six months
description: any complication for any line of treatments line
measure: anti- nuclear antibodies role
time frame: before enrollment
description: Detecting the predictors for chronic ITP especially ANA role
measure: Anti-platelets antibodies role
time frame: after6 months
description: Evaluation of the effect of the proposed drugs on the level of anti-platelet antibodies .
measure: Health quality life
time frame: after 6 months of treatment
description: The Arabic version of the 36-Item Short Form Survey Instrument (SF-36) questionnaire will be administered to all patients before & after treatment.
This questionnaire is a validated one which assesses general health functioning .
arm group label: hydroxychloroquine group
arm group type: Experimental
description: hydroxychloroquine tablets 200mg ,two times/day for at least 6 month
arm group label: vincristine group
arm group type: Active Comparator
description: vincristine ampoule , 1mg/ week, I.v drep over 2 hours for 4 weeks
arm group label: azathioprine group
arm group type: Active Comparator
description: azathioprine tablet 50mg, dose 100-150 mg daily for 6 month
intervention type: Drug
intervention name: Hydroxychloroquine
description: 200mg twice daily orally for at least 12 weeks
arm group label: hydroxychloroquine group
intervention type: Drug
intervention name: vincristine
description: 1mg intravenous weekly for 4 weeks
arm group label: vincristine group
intervention type: Drug
intervention name: azathioprine
description: dose 100mg daily for at least 3 weeks
arm group label: azathioprine group
other name: imuran
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Egypt
citation: Park YH, Yi HG, Lee MH, Kim CS, Lim JH. Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study. Int J Hematol. 2016 Feb;103(2):180-8. doi: 10.1007/s12185-015-1903-0. Epub 2015 Nov 20.
PMID: 26588926
citation: Poudyal BS, Sapkota B, Shrestha GS, Thapalia S, Gyawali B, Tuladhar S. Safety and Efficacy of Azathioprine as a Second Line Therapy for Primary Immune Thrombocytopenic Purpura. JNMA J Nepal Med Assoc. 2016 Jul-Sep;55(203):16-21.
PMID: 27935917
citation: Cooper N. State of the art - how I manage immune thrombocytopenia. Br J Haematol. 2017 Apr;177(1):39-54. doi: 10.1111/bjh.14515. Epub 2017 Mar 10. Erratum In: Br J Haematol. 2017 May;177(4):661.
PMID: 28295192
citation: Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur J Haematol Suppl. 2009 Mar;(71):3-7. doi: 10.1111/j.1600-0609.2008.01206.x.
PMID: 19200301
citation: Khellaf M, Chabrol A, Mahevas M, Roudot-Thoraval F, Limal N, Languille L, Bierling P, Michel M, Godeau B. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies. Am J Hematol. 2014 Feb;89(2):194-8. doi: 10.1002/ajh.23609. Epub 2013 Nov 20.
PMID: 24254965
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Ghada E. M. Abdallah
investigator title: Principal investegator
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Hydroxychloroquine
mesh term: Vincristine
mesh term: Azathioprine
sharing ipd: No