<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/NCT03771378</url>
  </required_header>
  <id_info>
    <org_study_id>T18008-A</org_study_id>
    <nct_id>NCT03771378</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of rhTPO and Eltrombopag in Patients With Primary Immune Thrombocytopenia (ITP)</brief_title>
  <acronym>(ITP;rhTPO)</acronym>
  <official_title>Efficacy and Safety of rhTPO and Eltrombopag in the Treatment of Chinese Adults With Primary Immune Thrombocytopenia (ITP):a Multicenter, Double-blind, Randomized, Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wuhan Union Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital of Nanchang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Third Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First People's Hospital of Yuhang District</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xiangyang Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Wuhan Union Hospital, China</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. In most&#xD;
      cases, platelet count is negatively correlated with the severity of bleeding. Correcting low&#xD;
      platelets is the main measure to prevent bleeding in patients with ITP. Both rhTPO and&#xD;
      eltrombopag act on TPO receptors to increase platelets.Which one will have a better&#xD;
      short-term (2 weeks) effect to improve platelets is the purpose of the investigator's&#xD;
      research.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. ITP&#xD;
      patients have an increased risk of bleeding and the clinical symptoms are petechia,&#xD;
      ecchymosis, organ hemorrhage and even life-threatening bleeding. The mortality rate in ITP is&#xD;
      increased approximately 60% compared with age- and sex matched comparisons, bleeding is one&#xD;
      of the leading causes of death, thus treating and preventing bleeding is particularly&#xD;
      important for those patients. In most cases, platelet count is negatively correlated with the&#xD;
      severity of bleeding. Correcting low platelets is the main measure to prevent bleeding in&#xD;
      patients with ITP. Recombinant human thrombopoietin (rhTPO), a full-length glycated TPO, is a&#xD;
      recombinant form of c-Mpl ligand that competes with endogenous TPO for binding to TPO&#xD;
      receptors (TPO-R, c-Mp0), many clinical trials have shown that rhTPO can efficiently and&#xD;
      safely stimulate platelet production, increase peripheral blood platelet count. The State&#xD;
      Food and Drug Administration approved the drug as the second-line treatment for patients with&#xD;
      ITP in 2005. Eltrombopag is an oral, synthetic non-peptide small molecule human&#xD;
      thrombopoietin receptor agonist approved by the US FDA in November 2008 for the treatment of&#xD;
      patients with chronic ITP, which were inefficiently by use of glucocorticoids, immunoglobulin&#xD;
      or splenectomy. However, pharmacokinetic study of eltrombopag showed that Asians have twice&#xD;
      the drug exposure rate than non-Asians, so eltrombopag may have different effects in&#xD;
      different populations. Therefore, this trial will compare the efficacy and safety of&#xD;
      intravenous rhTPO or oral use of eltrombopag after 14 days of treatment in Chinese ITP&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Anticipated">May 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2020</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>
    <intervention_model_description>This study was a randomized, double-blind trial in which patients were divided into two groups, one receiving rhTPO injection and oral placebo tablet; the other group receiving oral eltrombopag and receiving a injection placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment response</measure>
    <time_frame>14 days from treatment</time_frame>
    <description>Proportion of subjects with platelet counts ≥50×10^9/L after 14 days of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Remission rate</measure>
    <time_frame>14 days from treatment</time_frame>
    <description>Complete response(platelet count ≥100 X 109/L and absence of bleeding), effective(platelet count&#xD;
≥30X109/L and at least 2-fold increase of the baseline count and absence of bleeding), ineffective(platelet count &lt;30 X109/L or less than 2-fold increase of the baseline platelet count or bleeding) proportion of testers after 14 days of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug efficacy: Evaluation of effectiveness</measure>
    <time_frame>14 days from treatment</time_frame>
    <description>During treatment, the proportion of subjects, which the platelet count at least once reached ≥50×109/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of effectiveness: the proportion of subjects, which the platelet count increased at least 2 times compared with baseline</measure>
    <time_frame>14 days from treatment</time_frame>
    <description>During treatment, the proportion of subjects, which the platelet count increased at least 2 times compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Using ITP-specific bleeding assessment tool (ITP-BAT) to accessvbleeding scoer</measure>
    <time_frame>1 month from treatment</time_frame>
    <description>Bleeding manifestations were grouped into three major domains: skin (S), visible mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any fatal bleeding.&#xD;
Bleeding reported by the patient without medical documentation is graded 1. Within each domain, the same grade is assigned to bleeding manifestations of similar clinical impact. The &quot;worst bleeding manifestation since the last visit&quot; (observation period) is graded (a suitable database collection form is provided), and the highest grade within each domain is recorded.bleeding score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of adverse events</measure>
    <time_frame>14 days from treatment</time_frame>
    <description>During treatment, the proportion of subjects, which received at least once rescue.Adverse events were evaluated according to Common Terminology Criteria for Adverse Events,version3.0,published by US National Cancer Institute.Adverse events included liver injury, fever, headache, bleeding, abdominal pain, nausea, vomiting, etc</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of side effects of the drugs</measure>
    <time_frame>1 month from treatment</time_frame>
    <description>Assessing safety through the adverse events,such as liver damage, etc.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Primary Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Effective of rhTPO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After enrollment, all subjects receive rhTPO, the dose is 300 U / Kg, s.c. qd, blood routine examination is detected every 3 days during treatment. If the platelet count &gt; 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will receive a mimetic (tablet), po, qd.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Effective of eltrombopag</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After enrollment, all subjects receive eltrombopag, the dose is 25 mg/day, po, qd, blood routine examination is detected every 3 days during treatment. If the platelet count &gt; 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will give a mimetic (injection), at a dose of 300 U/Kg, s.c. qd.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhTPO</intervention_name>
    <description>After enrollment, all subjects receive TPO, the dose is 300 U / Kg, s.c. qd, blood routine examination is detected every 3 days during treatment. If the platelet count &gt; 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will receive a mimetic (tablet), po, qd.</description>
    <arm_group_label>Effective of rhTPO</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>eltrombopag</intervention_name>
    <description>After enrollment, all subjects receive eltrombopag, the dose is 25 mg/day, po, qd. blood routine examination is detected every 3 days during treatment. If the platelet count &gt; 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will give a mimetic (injection), at a dose of 300 U/Kg, s.c. qd.</description>
    <arm_group_label>Effective of eltrombopag</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient signs an informed consent form.&#xD;
&#xD;
          2. Age from 18 to 75 years old&#xD;
&#xD;
          3. The patient's first diagnosis of ITP is at least 6 months before enrollment; the&#xD;
             platelet count must &lt;30×109/L before taking the study drug (48 hours before).&#xD;
&#xD;
          4. Patients who were diagnosed with ITP by bone marrow biopsy and other related&#xD;
             examinations before enrollment(Bone marrow biopsy is valid for 30 days, including 30&#xD;
             days);&#xD;
&#xD;
          5. The patient has been treated with splenectomy for relapse or relapse; or the patient&#xD;
             has not undergone splenectomy, but was ineffective or relapses after treatment with at&#xD;
             least one first line drug. Past ITP therapy can include, but is not limited to,&#xD;
             corticosteroids, immunoglobulins (IVIG or anti-D Immunoglobulin), azathioprine,&#xD;
             danazol, cyclophosphamide and immunomodulators;&#xD;
&#xD;
          6. Previous salvage treatments included infusion of platelets, immunoglobulins,&#xD;
             immunomodulators, and cyclophosphamide must be completed 2 weeks prior to enrollment&#xD;
             or treatment. Corticosteroids must end at least 14 days before enrollment.&#xD;
&#xD;
          7. Patients receiving immunosuppressive agents (including corticosteroids, azathioprine,&#xD;
             danazol, cyclosporin A, mycophenolate mofetil) or proprietary Chinese medicines have&#xD;
             maintained a stable therapeutic dose for at least the last month; patients who&#xD;
             received rituximab should be discontinued half a year prior to enrollment; patients&#xD;
             with spleen were enrolled six months after surgery;&#xD;
&#xD;
          8. No heart disease in the past 3 months, including NYHA grade III/IV charge&#xD;
&#xD;
             , heart failure, arrhythmia or myocardial infarction requiring medical treatment;&#xD;
&#xD;
          9. Laboratory tests for coagulation function showed that prothrombin time (PT/INR) and&#xD;
             activated partial thromboplastin time (APTT) values did not exceed 20% of the normal&#xD;
             reference range.No history of coagulation abnormalities except ITP;&#xD;
&#xD;
         10. White blood cell count, neutrophil absolute value, hemoglobin in the normal&#xD;
             value.Except in the following cases: a) Platelet count &lt;30×10^9/L within Day1 or Day1&#xD;
             within 48 hours; b) Hemoglobin: if anemia is clearly caused by ITP (thrombocytopenia&#xD;
             caused blood loss), the lower limit of the subject's hemoglobin level below the normal&#xD;
             value can be based on the investigator's judgment to decide the subject whether to be&#xD;
             selected; c) absolute neutrophil count ≥ 1.5 × 109 / L can be enrolled;&#xD;
&#xD;
         11. The following clinical biochemical indicators must be within 20% of the normal range:&#xD;
             creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin and&#xD;
             alkaline phosphatase. In addition, serum albumin is not lower than the lower limit of&#xD;
             normal value by 10%;&#xD;
&#xD;
         12. Subjects took an approved method of contraception. Female subjects (or female partners&#xD;
             of male subjects) must be infertile (hysterectomy, bilateral salpingectomy, bilateral&#xD;
             tubal ligation or more than 1 year after menopause) or have fertility but before the&#xD;
             first dose for 2 weeks, study-approved contraceptive methods were used throughout the&#xD;
             study period to 28 days after the end of the study or discontinuation of the&#xD;
             study.Male subjects with a fertile female partner must have undergone vasectomy or&#xD;
             consent to effective contraception throughout the study period (2 weeks prior to the&#xD;
             first dose, throughout the study period, until the end of the study or 28 days after&#xD;
             the discontinuation of the study) method;&#xD;
&#xD;
         13. Women with fertility must have a negative serum pregnancy test within 24 hours prior&#xD;
             to the first dose;&#xD;
&#xD;
         14. Subjects fully understand and are able to comply with the requirements of the research&#xD;
             protocol and are willing to complete the study as planned.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects had a history of any arterial/venous thrombosis (including stroke, transient&#xD;
             ischemic attack, myocardial infarction, deep vein thrombosis, or pulmonary embolism)&#xD;
             and had at least 2 of the following risk factors: hormone replacement therapy, oral&#xD;
             contraception medicine (including estrogen), smoking, diabetes, hypercholesterolemia,&#xD;
             drug-controlled hypertension, malignant tumors, hereditary coagulopathy;&#xD;
&#xD;
          2. Abnormalities other than ITP during the screening phase or any medical history or&#xD;
             condition that the investigator considered unsuitable for participation in the study;&#xD;
&#xD;
          3. Patients with BMI ≥ 28;&#xD;
&#xD;
          4. Pregnant or lactating women;&#xD;
&#xD;
          5. A history of alcohol/drug abuse within 12 months prior to screening or first dose;&#xD;
&#xD;
          6. Previous treatment with a specific study drug other than rhTPO or other research&#xD;
             treatments;&#xD;
&#xD;
          7. The subject has previously received or is currently receiving treatment with exenatide&#xD;
             or other thrombopoietin receptor agonists;&#xD;
&#xD;
          8. Throughout the study, medications that affected platelet function (including but not&#xD;
             limited to aspirin, clopidogrel and/or non-steroidal anti-inflammatory drugs NSAIDs)&#xD;
             or anticoagulant therapy were continued for &gt;3 days;&#xD;
&#xD;
          9. Accept any herbal or nutritional supplements, excluding vitamin supplements and&#xD;
             mineral supplements within 1 week prior to the start of the study;&#xD;
&#xD;
         10. There is a history of abnormal platelet aggregation that may affect the reliability of&#xD;
             platelet count measurements;&#xD;
&#xD;
         11. Before the first dose administration, the bone marrow biopsy showed abnormality except&#xD;
             for ITP within 4 weeks, and the investigator judged that the abnormality made the&#xD;
             subject unsuitable for the study, or the bone marrow biopsy showed other primary&#xD;
             disease which caused thrombocytopenia;&#xD;
&#xD;
         12. Evidence of all laboratory or clinical HIV infections, previous clinical history of&#xD;
             hepatitis C,hepatitis B, or active hepatitis at screening. Laboratory tests during the&#xD;
             screening period indicate hepatitis C infection or hepatitis B infection. (Defined as&#xD;
             HBsAg test positive, in addition, if the HBsAg test is negative, but HBcAb is&#xD;
             positive, regardless of the status of HBsAb, HBV DNA testing is required, if positive,&#xD;
             subjects should be excluded);&#xD;
&#xD;
         13. Rescuing treatment is required before the first dose of the drug.&#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>Hu Yu, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wuhan Union Hospital, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hu Yu, M.D., Ph.D</last_name>
    <phone>86-13986183871</phone>
    <phone_ext>8613986183871</phone_ext>
    <email>dr_huyu@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mei Heng, M.D., Ph.D</last_name>
    <phone>86-13886160811</phone>
    <phone_ext>8613986183871</phone_ext>
    <email>mayheng@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Zhou Yiming</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430074</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>zhou ming</last_name>
      <phone>+8613212794115</phone>
      <email>xumin_1015@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Xu MIN</last_name>
      <phone>+8613212794115</phone>
      <email>xumin_1015@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <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>Hodak E, David M, Ingber A, Rotem A, Hazaz B, Shamai-Lubovitz O, Sandbank M. The clinical and histopathological spectrum of IgA-pemphigus--report of two cases. Clin Exp Dermatol. 1990 Nov;15(6):433-7. doi: 10.1111/j.1365-2230.1990.tb02138.x.</citation>
    <PMID>2279341</PMID>
  </results_reference>
  <results_reference>
    <citation>Zhang Y, Kolesar JM. Eltrombopag: an oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. Clin Ther. 2011 Nov;33(11):1560-76. doi: 10.1016/j.clinthera.2011.10.004. Epub 2011 Nov 4.</citation>
    <PMID>22054810</PMID>
  </results_reference>
  <results_reference>
    <citation>Erickson-Miller CL, DeLorme E, Tian SS, Hopson CB, Stark K, Giampa L, Valoret EI, Duffy KJ, Luengo JL, Rosen J, Miller SG, Dillon SB, Lamb P. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol. 2005 Jan;33(1):85-93. doi: 10.1016/j.exphem.2004.09.006.</citation>
    <PMID>15661401</PMID>
  </results_reference>
  <results_reference>
    <citation>Williams DD, Peng B, Bailey CK, Wire MB, Deng Y, Park JW, Collins DA, Kapsi SG, Jenkins JM. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther. 2009 Apr;31(4):764-76. doi: 10.1016/j.clinthera.2009.04.010.</citation>
    <PMID>19446149</PMID>
  </results_reference>
  <results_reference>
    <citation>Cheng G. Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile. Ther Adv Hematol. 2012 Jun;3(3):155-64. doi: 10.1177/2040620712442525.</citation>
    <PMID>23556122</PMID>
  </results_reference>
  <results_reference>
    <citation>Tomiyama Y, Miyakawa Y, Okamoto S, Katsutani S, Kimura A, Okoshi Y, Ninomiya H, Kosugi H, Nomura S, Ozaki K, Ikeda Y, Hattori T, Katsura K, Kanakura Y. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost. 2012 May;10(5):799-806. doi: 10.1111/j.1538-7836.2012.04695.x.</citation>
    <PMID>22409309</PMID>
  </results_reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>November 14, 2019</last_update_submitted>
  <last_update_submitted_qc>November 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Wuhan Union Hospital, China</investigator_affiliation>
    <investigator_full_name>MEI HENG</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>ITP</keyword>
  <keyword>rhTPO</keyword>
  <keyword>Eltrombopag</keyword>
  <keyword>platelets</keyword>
  <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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>It is not clear whether the data would involve patient privacy or whether patients would agree to the disclosure of the data.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT03771378/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03771378
org study id: T18008-A
nct id: NCT03771378
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. In most
      cases, platelet count is negatively correlated with the severity of bleeding. Correcting low
      platelets is the main measure to prevent bleeding in patients with ITP. Both rhTPO and
      eltrombopag act on TPO receptors to increase platelets.Which one will have a better
      short-term (2 weeks) effect to improve platelets is the purpose of the investigator's
      research.
Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. ITP
      patients have an increased risk of bleeding and the clinical symptoms are petechia,
      ecchymosis, organ hemorrhage and even life-threatening bleeding. The mortality rate in ITP is
      increased approximately 60% compared with age- and sex matched comparisons, bleeding is one
      of the leading causes of death, thus treating and preventing bleeding is particularly
      important for those patients. In most cases, platelet count is negatively correlated with the
      severity of bleeding. Correcting low platelets is the main measure to prevent bleeding in
      patients with ITP. Recombinant human thrombopoietin (rhTPO), a full-length glycated TPO, is a
      recombinant form of c-Mpl ligand that competes with endogenous TPO for binding to TPO
      receptors (TPO-R, c-Mp0), many clinical trials have shown that rhTPO can efficiently and
      safely stimulate platelet production, increase peripheral blood platelet count. The State
      Food and Drug Administration approved the drug as the second-line treatment for patients with
      ITP in 2005. Eltrombopag is an oral, synthetic non-peptide small molecule human
      thrombopoietin receptor agonist approved by the US FDA in November 2008 for the treatment of
      patients with chronic ITP, which were inefficiently by use of glucocorticoids, immunoglobulin
      or splenectomy. However, pharmacokinetic study of eltrombopag showed that Asians have twice
      the drug exposure rate than non-Asians, so eltrombopag may have different effects in
      different populations. Therefore, this trial will compare the efficacy and safety of
      intravenous rhTPO or oral use of eltrombopag after 14 days of treatment in Chinese ITP
      patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study was a randomized, double-blind trial in which patients were divided into two groups, one receiving rhTPO injection and oral placebo tablet; the other group receiving oral eltrombopag and receiving a injection placebo.
primary purpose: Treatment
masking: Single (Investigator)
measure: Treatment response
time frame: 14 days from treatment
description: Proportion of subjects with platelet counts ≥50×10^9/L after 14 days of treatment
measure: Remission rate
time frame: 14 days from treatment
description: Complete response(platelet count ≥100 X 109/L and absence of bleeding), effective(platelet count
≥30X109/L and at least 2-fold increase of the baseline count and absence of bleeding), ineffective(platelet count <30 X109/L or less than 2-fold increase of the baseline platelet count or bleeding) proportion of testers after 14 days of treatment
measure: Drug efficacy: Evaluation of effectiveness
time frame: 14 days from treatment
description: During treatment, the proportion of subjects, which the platelet count at least once reached ≥50×109/L.
measure: Evaluation of effectiveness: the proportion of subjects, which the platelet count increased at least 2 times compared with baseline
time frame: 14 days from treatment
description: During treatment, the proportion of subjects, which the platelet count increased at least 2 times compared with baseline.
measure: Using ITP-specific bleeding assessment tool (ITP-BAT) to accessvbleeding scoer
time frame: 1 month from treatment
description: Bleeding manifestations were grouped into three major domains: skin (S), visible mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any fatal bleeding.
Bleeding reported by the patient without medical documentation is graded 1. Within each domain, the same grade is assigned to bleeding manifestations of similar clinical impact. The "worst bleeding manifestation since the last visit" (observation period) is graded (a suitable database collection form is provided), and the highest grade within each domain is recorded.bleeding score
measure: The incidence of adverse events
time frame: 14 days from treatment
description: During treatment, the proportion of subjects, which received at least once rescue.Adverse events were evaluated according to Common Terminology Criteria for Adverse Events,version3.0,published by US National Cancer Institute.Adverse events included liver injury, fever, headache, bleeding, abdominal pain, nausea, vomiting, etc
measure: The incidence of side effects of the drugs
time frame: 1 month from treatment
description: Assessing safety through the adverse events,such as liver damage, etc.
arm group label: Effective of rhTPO
arm group type: Experimental
description: After enrollment, all subjects receive rhTPO, the dose is 300 U / Kg, s.c. qd, blood routine examination is detected every 3 days during treatment. If the platelet count > 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will receive a mimetic (tablet), po, qd.
arm group label: Effective of eltrombopag
arm group type: Active Comparator
description: After enrollment, all subjects receive eltrombopag, the dose is 25 mg/day, po, qd, blood routine examination is detected every 3 days during treatment. If the platelet count > 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will give a mimetic (injection), at a dose of 300 U/Kg, s.c. qd.
intervention type: Drug
intervention name: rhTPO
description: After enrollment, all subjects receive TPO, the dose is 300 U / Kg, s.c. qd, blood routine examination is detected every 3 days during treatment. If the platelet count > 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will receive a mimetic (tablet), po, qd.
arm group label: Effective of rhTPO
intervention type: Drug
intervention name: eltrombopag
description: After enrollment, all subjects receive eltrombopag, the dose is 25 mg/day, po, qd. blood routine examination is detected every 3 days during treatment. If the platelet count > 250 × 109 / L, the drug will stop until the platelet count ≤ 100 × 109 / L. Efficacy and safety will be evaluated on day 15. The evaluation criteria were based on the consensus of ITP. At the same time, all subjects will give a mimetic (injection), at a dose of 300 U/Kg, s.c. qd.
arm group label: Effective of eltrombopag
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hu Yu, M.D., Ph.D
role: Principal Investigator
affiliation: Wuhan Union Hospital, China
last name: Hu Yu, M.D., Ph.D
phone: 86-13986183871
phone ext: 8613986183871
email: dr_huyu@126.com
last name: Mei Heng, M.D., Ph.D
phone: 86-13886160811
phone ext: 8613986183871
email: mayheng@126.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
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PMID: 19005182
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citation: Zhang Y, Kolesar JM. Eltrombopag: an oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. Clin Ther. 2011 Nov;33(11):1560-76. doi: 10.1016/j.clinthera.2011.10.004. Epub 2011 Nov 4.
PMID: 22054810
citation: Erickson-Miller CL, DeLorme E, Tian SS, Hopson CB, Stark K, Giampa L, Valoret EI, Duffy KJ, Luengo JL, Rosen J, Miller SG, Dillon SB, Lamb P. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol. 2005 Jan;33(1):85-93. doi: 10.1016/j.exphem.2004.09.006.
PMID: 15661401
citation: Williams DD, Peng B, Bailey CK, Wire MB, Deng Y, Park JW, Collins DA, Kapsi SG, Jenkins JM. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther. 2009 Apr;31(4):764-76. doi: 10.1016/j.clinthera.2009.04.010.
PMID: 19446149
citation: Cheng G. Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile. Ther Adv Hematol. 2012 Jun;3(3):155-64. doi: 10.1177/2040620712442525.
PMID: 23556122
citation: Tomiyama Y, Miyakawa Y, Okamoto S, Katsutani S, Kimura A, Okoshi Y, Ninomiya H, Kosugi H, Nomura S, Ozaki K, Ikeda Y, Hattori T, Katsura K, Kanakura Y. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost. 2012 May;10(5):799-806. doi: 10.1111/j.1538-7836.2012.04695.x.
PMID: 22409309
responsible party type: Principal Investigator
investigator affiliation: Wuhan Union Hospital, China
investigator full name: MEI HENG
investigator title: Associate Professor
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic
sharing ipd: Undecided
ipd description: It is not clear whether the data would involve patient privacy or whether patients would agree to the disclosure of the data.
provided document: 