<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/NCT01734057</url>
  </required_header>
  <id_info>
    <org_study_id>ITP-008</org_study_id>
    <nct_id>NCT01734057</nct_id>
  </id_info>
  <brief_title>Recombinant Human Thrombopoietin (rhTPO) Combining Rituximab Versus High-dose Dexamethasone for Initial Treatment of Primary Immune Thrombocytopenia (ITP)</brief_title>
  <official_title>A Multicentre Investigation of Recombinant Human Thrombopoietin (rhTPO) Combining Rituximab Versus High-dose Dexamethasone for Initial Treatment of Primary Immune Thrombocytopenia (ITP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Affiliated Hospital of the Chinese Academy of Military Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Anhui Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Dalian Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shandong Provincial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China Medical University, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Provincial Hospital of TCM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shandong University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The project was undertaking by Qilu Hospital of Shandong University and other 13 well-known&#xD;
      hospitals in China. In order to report the efficacy and safety of Recombinant Human&#xD;
      thrombopoietin combining with Rituximab for the treatment of adults with primary immune&#xD;
      thrombocytopenia (ITP), compared to conventional high-dose dexamethasone therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators are undertaking a parallel group, multicentre, randomised controlled trial&#xD;
      of 240 primary ITP adult patients from 14 medical centers in China. One part of the&#xD;
      participants are randomly selected to receive recombinant human thrombopoietin (given&#xD;
      subcutaneously at a dose of 300Units/kgfor 14 consecutive days, following with a flexible&#xD;
      dosage depending on platelet count until the 28th day), combining with rituximab (given&#xD;
      intravenously at a dose of 100 mg weekly for 4 weeks, i.e. Day 1, 8, 15, 22; the others are&#xD;
      selected to receive high-dose of dexamethasone treatment (given intravenously at a dose of 40&#xD;
      mg daily for 4 days). Platelet count was evaluated before and after treatment,in order to&#xD;
      report the conversion ratio of primary ITP to chronic ITP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No eligible patient was enrolled.&#xD;
  </why_stopped>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">October 2013</completion_date>
  <primary_completion_date type="Anticipated">July 2013</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of platelet response(Chronic ITP)</measure>
    <time_frame>up to 1 year per subject</time_frame>
    <description>Chronic ITP is defined as having platelet count less than 100×10^9/L,lasting for more than 12 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of platelet response (Complete Response)</measure>
    <time_frame>up to 1 year per subject</time_frame>
    <description>CR. A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L without recurrence of thrombocytopenia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of platelet response (R)</measure>
    <time_frame>up to 1 year per subject</time_frame>
    <description>R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Purpura</condition>
  <condition>Idiopathic Thrombocytopenic Purpura</condition>
  <arm_group>
    <arm_group_label>combinant treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>120 enrolled patients are randomly picked up to take Rituximab in combination with rhTPO at the indicated dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>single treatment group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>120 enrolled patients are randomly picked up to take dexamethasone at the indicated dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>recombinant human thrombopoietin (rhTPO); rituximab</intervention_name>
    <description>patients in recombination treatment group take Rituximab( intravenously ,100 mg weekly for 4 consecutive weeks); in combination with rhTPO( subcutaneously , 300U/kg for 14 consecutive days,followed by flexible treating dosage so as to keep the platelet count above 50×10^9/L until the 28th day)</description>
    <arm_group_label>combinant treatment group</arm_group_label>
    <other_name>Recombinant Human Thrombopoietin</other_name>
    <other_name>Recombinant Human TPO</other_name>
    <other_name>rhTPO combine with Rituximab</other_name>
    <other_name>Recombinant Human Thrombopoietin combine with Rituximab</other_name>
    <other_name>Recombinant Human TPO combine with Rituximab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Patients in single treatment group take dexamethasone intravenously at 40 mg daily for 4 consecutive days.</description>
    <arm_group_label>single treatment group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Meet the diagnostic criteria for immune thrombocytopenia.&#xD;
&#xD;
          2. Untreated hospitalized patients, may be male or female, between the ages of 18 ~ 80&#xD;
             years.&#xD;
&#xD;
          3. To show a platelet count &lt; 30×10^9/L, and with bleeding manifestations.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
&#xD;
          5. Willing and able to sign written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts&#xD;
             within 3 months before the screening visit.&#xD;
&#xD;
          2. Received high-dose steroids or intravenous immunoglobulin transfusion(IVIG) in the 3&#xD;
             weeks prior to the start of the study.&#xD;
&#xD;
          3. Current HIV infection or hepatitis B virus or hepatitis C virus infections.&#xD;
&#xD;
          4. Severe medical condition (lung, hepatic or renal disorder) other than ITP. Unstable or&#xD;
             uncontrolled disease or condition related to or impacting cardiac function (e.g.,&#xD;
             unstable angina, congestive heart failure, uncontrolled hypertension or cardiac&#xD;
             arrhythmia)&#xD;
&#xD;
          5. Female patients who are nursing or pregnant, who may be pregnant, or who contemplate&#xD;
             pregnancy during the study period.&#xD;
&#xD;
          6. Have a known diagnosis of other autoimmune diseases, established in the medical&#xD;
             history and laboratory findings with positive results for the determination of&#xD;
             antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct&#xD;
             Coombs test.&#xD;
&#xD;
          7. Patients who are deemed unsuitable for the study by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming Hou, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shandong University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Qilu Hospital, Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Medeot M, Zaja F, Vianelli N, Battista M, Baccarani M, Patriarca F, Soldano F, Isola M, De Luca S, Fanin R. Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. Eur J Haematol. 2008 Sep;81(3):165-9. doi: 10.1111/j.1600-0609.2008.01100.x. Epub 2008 May 27.</citation>
    <PMID>18510702</PMID>
  </results_reference>
  <results_reference>
    <citation>Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21.</citation>
    <PMID>19846889</PMID>
  </results_reference>
  <results_reference>
    <citation>Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.</citation>
    <PMID>19005182</PMID>
  </results_reference>
  <results_reference>
    <citation>Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. doi: 10.1056/NEJMoa030254.</citation>
    <PMID>12944568</PMID>
  </results_reference>
  <results_reference>
    <citation>Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. doi: 10.1182/blood-2005-12-015222. Epub 2006 Oct 31.</citation>
    <PMID>17077333</PMID>
  </results_reference>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>April 18, 2016</last_update_submitted>
  <last_update_submitted_qc>April 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 20, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong University</investigator_affiliation>
    <investigator_full_name>Ming Hou</investigator_full_name>
    <investigator_title>Professor and Director</investigator_title>
  </responsible_party>
  <keyword>Recombinant Human Thrombopoietin</keyword>
  <keyword>rhTPO</keyword>
  <keyword>Rituximab</keyword>
  <keyword>Dexamethasone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Purpura</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01734057
org study id: ITP-008
nct id: NCT01734057
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The project was undertaking by Qilu Hospital of Shandong University and other 13 well-known
      hospitals in China. In order to report the efficacy and safety of Recombinant Human
      thrombopoietin combining with Rituximab for the treatment of adults with primary immune
      thrombocytopenia (ITP), compared to conventional high-dose dexamethasone therapy.
The investigators are undertaking a parallel group, multicentre, randomised controlled trial
      of 240 primary ITP adult patients from 14 medical centers in China. One part of the
      participants are randomly selected to receive recombinant human thrombopoietin (given
      subcutaneously at a dose of 300Units/kgfor 14 consecutive days, following with a flexible
      dosage depending on platelet count until the 28th day), combining with rituximab (given
      intravenously at a dose of 100 mg weekly for 4 weeks, i.e. Day 1, 8, 15, 22; the others are
      selected to receive high-dose of dexamethasone treatment (given intravenously at a dose of 40
      mg daily for 4 days). Platelet count was evaluated before and after treatment,in order to
      report the conversion ratio of primary ITP to chronic ITP.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Evaluation of platelet response(Chronic ITP)
time frame: up to 1 year per subject
description: Chronic ITP is defined as having platelet count less than 100×10^9/L,lasting for more than 12 months.
measure: Evaluation of platelet response (Complete Response)
time frame: up to 1 year per subject
description: CR. A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L without recurrence of thrombocytopenia
measure: Evaluation of platelet response (R)
time frame: up to 1 year per subject
description: R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia
arm group label: combinant treatment group
arm group type: Experimental
description: 120 enrolled patients are randomly picked up to take Rituximab in combination with rhTPO at the indicated dose.
arm group label: single treatment group
arm group type: Active Comparator
description: 120 enrolled patients are randomly picked up to take dexamethasone at the indicated dose.
intervention type: Drug
intervention name: recombinant human thrombopoietin (rhTPO); rituximab
description: patients in recombination treatment group take Rituximab( intravenously ,100 mg weekly for 4 consecutive weeks); in combination with rhTPO( subcutaneously , 300U/kg for 14 consecutive days,followed by flexible treating dosage so as to keep the platelet count above 50×10^9/L until the 28th day)
arm group label: combinant treatment group
other name: Recombinant Human Thrombopoietin
other name: Recombinant Human TPO
other name: rhTPO combine with Rituximab
other name: Recombinant Human Thrombopoietin combine with Rituximab
other name: Recombinant Human TPO combine with Rituximab
intervention type: Drug
intervention name: Dexamethasone
description: Patients in single treatment group take dexamethasone intravenously at 40 mg daily for 4 consecutive days.
arm group label: single treatment group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ming Hou, Dr.
role: Principal Investigator
affiliation: Shandong University
facility: 
country: China
citation: Medeot M, Zaja F, Vianelli N, Battista M, Baccarani M, Patriarca F, Soldano F, Isola M, De Luca S, Fanin R. Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. Eur J Haematol. 2008 Sep;81(3):165-9. doi: 10.1111/j.1600-0609.2008.01100.x. Epub 2008 May 27.
PMID: 18510702
citation: Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21.
PMID: 19846889
citation: Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
PMID: 19005182
citation: Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. doi: 10.1056/NEJMoa030254.
PMID: 12944568
citation: Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. doi: 10.1182/blood-2005-12-015222. Epub 2006 Oct 31.
PMID: 17077333
responsible party type: Principal Investigator
investigator affiliation: Shandong University
investigator full name: Ming Hou
investigator title: Professor and Director
mesh term: Thrombocytopenia
mesh term: Purpura
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Purpura, Thrombocytopenic
mesh term: Dexamethasone
mesh term: Rituximab