<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/NCT04481282</url>
  </required_header>
  <id_info>
    <org_study_id>ITP-PKU010</org_study_id>
    <nct_id>NCT04481282</nct_id>
  </id_info>
  <brief_title>The Combination of Terbutaline and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia</brief_title>
  <official_title>The Combination of Terbutaline and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University People's Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Single-arm, open-label, single center study to assess the efficacy and safety of terbutaline&#xD;
      plus danazol in patients with corticosteroid resistant/relapsed ITP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients&#xD;
      achieve remission from first-line therapies. However, the underlying mechanism of&#xD;
      corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a&#xD;
      great challenge. β2-AR agonist terbutaline modulates T cell differentiation and effector cell&#xD;
      function.&#xD;
&#xD;
      A single center prospective study was performed in non-splenectomized ITP patients who were&#xD;
      either resistant to a standard dose of corticosteroids or had relapsed. Patients were&#xD;
      assigned to terbutaline plus danazol group. Platelet count, bleeding and other symptoms were&#xD;
      evaluated before and after treatment. Adverse events are also recorded throughout the study,&#xD;
      in order to assess the efficacy and safety of terbutaline plus danazol in patients with&#xD;
      corticosteroid-resistant/relapsed ITP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sustained response</measure>
    <time_frame>6 months</time_frame>
    <description>The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up. Interim analysis was scheduled at 50% through recruitment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>complete remission</measure>
    <time_frame>6 months</time_frame>
    <description>The number of participants (responders) with platelet count&gt;=100x10^9/L (CR) and the absence of bleeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>partial remission</measure>
    <time_frame>6 months</time_frame>
    <description>The number of participants (responders) with platelet count &gt;=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to response</measure>
    <time_frame>6 months</time_frame>
    <description>Time to response was defined as the time from starting treatment to the time to achieve the response. Interim analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of response</measure>
    <time_frame>6 months</time_frame>
    <description>Duration of response was measured from the achievement of response to the loss of response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of treatment-emergent adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Terbutaline plus Danazol group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Terbutaline 2.5mg tid po plus danazol 200mg bid po for 12weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Terbutaline</intervention_name>
    <description>2.5mg po tid for 12 weeks</description>
    <arm_group_label>Terbutaline plus Danazol group</arm_group_label>
    <other_name>Bricanyl Brethine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danazol</intervention_name>
    <description>200mg po bid for 12 weeks</description>
    <arm_group_label>Terbutaline plus Danazol group</arm_group_label>
    <other_name>Danocrine</other_name>
    <other_name>Cleregil</other_name>
    <other_name>Danol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ITP confirmed by excluding other supervened causes of thrombocytopenia;&#xD;
&#xD;
          -  Platelet count of less than 30×10^9/L at enrollment;&#xD;
&#xD;
          -  Patients who did not achieve a sustained response to treatment with full dose&#xD;
             corticosteroids for a minimum duration of 4 weeks or who relapsed during&#xD;
             steroid-tapering or after its discontinuation;&#xD;
&#xD;
          -  Subject has signed and dated written informed consent.&#xD;
&#xD;
          -  Fertile patients must use effective contraception during treatment and observational&#xD;
             period&#xD;
&#xD;
          -  Negative pregnancy test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori&#xD;
             infection or patients with systemic lupus erythematosus)&#xD;
&#xD;
          -  congestive heart failure&#xD;
&#xD;
          -  severe arrhythmia&#xD;
&#xD;
          -  nursing or pregnant women&#xD;
&#xD;
          -  aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the&#xD;
             normal threshold criteria&#xD;
&#xD;
          -  creatinine or serum bilirubin levels each 1•5 times or more than the normal range&#xD;
&#xD;
          -  active or previous malignancy&#xD;
&#xD;
          -  Unable to do blood routine test for the sake of time, distance, economic issues or&#xD;
             other reasons.&#xD;
&#xD;
          -  diagnosis with any of the following diseases: chronic hypertension, hyperthyroidism,&#xD;
             diabetes, or seizure disorder.&#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>Xiaohui Zhang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University People's Hospital, Peking University Insititute of Hematology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiaohui Zhang, MD</last_name>
    <phone>010-88324981</phone>
    <email>zhangxh100@sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gaochao Zhang, phD</last_name>
    <phone>+8618053803755</phone>
    <email>zhanggaochao0210@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking University Insititute of Hematology, Peking University People's Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100010</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaohui Zhang</last_name>
      <email>zhangxh100@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University People's Hospital</investigator_affiliation>
    <investigator_full_name>Xiao Hui Zhang</investigator_full_name>
    <investigator_title>Vice president of Peking Univeristy Institute of Hematology</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>Terbutaline</mesh_term>
    <mesh_term>Danazol</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/NCT04481282
org study id: ITP-PKU010
nct id: NCT04481282
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Single-arm, open-label, single center study to assess the efficacy and safety of terbutaline
      plus danazol in patients with corticosteroid resistant/relapsed ITP.
Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients
      achieve remission from first-line therapies. However, the underlying mechanism of
      corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a
      great challenge. β2-AR agonist terbutaline modulates T cell differentiation and effector cell
      function.

      A single center prospective study was performed in non-splenectomized ITP patients who were
      either resistant to a standard dose of corticosteroids or had relapsed. Patients were
      assigned to terbutaline plus danazol group. Platelet count, bleeding and other symptoms were
      evaluated before and after treatment. Adverse events are also recorded throughout the study,
      in order to assess the efficacy and safety of terbutaline plus danazol in patients with
      corticosteroid-resistant/relapsed ITP.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained response
time frame: 6 months
description: The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up. Interim analysis was scheduled at 50% through recruitment.
measure: complete remission
time frame: 6 months
description: The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding.
measure: partial remission
time frame: 6 months
description: The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy.
measure: time to response
time frame: 6 months
description: Time to response was defined as the time from starting treatment to the time to achieve the response. Interim analysis
measure: duration of response
time frame: 6 months
description: Duration of response was measured from the achievement of response to the loss of response.
measure: incidence of treatment-emergent adverse events
time frame: 6 months
description: Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
arm group label: Terbutaline plus Danazol group
arm group type: Experimental
description: Terbutaline 2.5mg tid po plus danazol 200mg bid po for 12weeks
intervention type: Drug
intervention name: Terbutaline
description: 2.5mg po tid for 12 weeks
arm group label: Terbutaline plus Danazol group
other name: Bricanyl Brethine
intervention type: Drug
intervention name: Danazol
description: 200mg po bid for 12 weeks
arm group label: Terbutaline plus Danazol group
other name: Danocrine
other name: Cleregil
other name: Danol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiaohui Zhang, MD
role: Principal Investigator
affiliation: Peking University People's Hospital, Peking University Insititute of Hematology
last name: Xiaohui Zhang, MD
phone: 010-88324981
email: zhangxh100@sina.com
last name: Gaochao Zhang, phD
phone: +8618053803755
email: zhanggaochao0210@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University People's Hospital
investigator full name: Xiao Hui Zhang
investigator title: Vice president of Peking Univeristy Institute of Hematology
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Terbutaline
mesh term: Danazol