<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/NCT01727193</url>
  </required_header>
  <id_info>
    <org_study_id>ZS-LEF</org_study_id>
    <nct_id>NCT01727193</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy</brief_title>
  <official_title>The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital, Sun Yat-Sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized controlled clinical study. The investigators screen of eligible&#xD;
      patients, randomized divide into the following two groups: corticosteroids + azathioprine&#xD;
      group, corticosteroids + leflunomide group. The investigators treat the enrolled patients,&#xD;
      estimate efficacy and observed the side effects according to the requirements of program. The&#xD;
      investigators establish a clinical database for recording patients date and statistical&#xD;
      analysis. Evaluation of short-term and long-term efficacy of thymectomized myasthenia gravis&#xD;
      patients in the different group prove that what kind of treatment can improve the cure rate.&#xD;
      The investigators will evaluate the acute toxicity (gastrointestinal side effects, liver and&#xD;
      kidney dysfunction) and long-term toxicity (immune dysfunction, gonadal suppression) when the&#xD;
      investigators apply these therapy in the treatment of different clinical types of myasthenia&#xD;
      gravis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">November 18, 2021</completion_date>
  <primary_completion_date type="Actual">October 18, 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the percent of achieving good response</measure>
    <time_frame>144 weeks</time_frame>
    <description>Pharmacologic Remission (PR) was the primary efficacy endpoint observed. Record the time the patient appears from the time of medication to the time of PR, and calculate the percentage of PR patients in each arm. Criteria for PR: The patient has had no symptoms or signs of MG for at least 1 year and continues to take some form of therapy for MG. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted. Patients taking cholinesterase inhibitors are excluded from this category because their use suggests the presence of weakness.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The changes of the disease severity and the antibody titer during the follow-up</measure>
    <time_frame>144 weeks</time_frame>
    <description>The magnitude by which QMG or ADL scores are reduced. Total amount of steroid used during the follow-up. Level of the acetylcholine receptor antibody.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">290</enrollment>
  <condition>Myasthenia Gravis</condition>
  <arm_group>
    <arm_group_label>Azathioprine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>cholinesterase inhibitors+Glucocorticoid +Azathioprine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Leflunomide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>cholinesterase inhibitors+glucocorticoid+Leflunomide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azathioprine</intervention_name>
    <description>The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 1 glucocorticoid + Azathioprine: Glucocorticoid (0.25mg/kg/d )plus Azathioprine at a starting dose of 50mg/d for 14 days, then increase up to 2mg/kg in 2 weeks.If no adverse events occurred , maintain the dose until 48 weeks.</description>
    <arm_group_label>Azathioprine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leflunomide</intervention_name>
    <description>The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 2 glucocorticoid + Leflunomide: Glucocorticoid (0.25mg/kg/d )plus Leflunomide 20mg/d for adult, 10mg/d for child. if no adverse events occurred , maintain the dose until 48 weeks.</description>
    <arm_group_label>Leflunomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 12 to 65 years；&#xD;
&#xD;
          2. Myasthenia gravis:&#xD;
&#xD;
               1. Patients who are diagnosed as generalized or ocular myasthenia gravis&#xD;
&#xD;
               2. have experienced extended thymectomy (including thymic hyperplasia and thymoma)，&#xD;
                  no significant complications in 6 months after operation , and does not received&#xD;
                  any immunosuppressants or glucocorticoids treatments.&#xD;
&#xD;
               3. do not applied in plasmapheresis or immunoglobulins treatment during 3 months .&#xD;
&#xD;
               4. women of child-bearing period do not have a plan of pregnant for at least 3 year.&#xD;
&#xD;
               5. Written consent of the patient, after informing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The liver , kidney or glycometabolic function is abnormal&#xD;
&#xD;
          2. Seriously complications, such as infection or symptom in central nervous system,&#xD;
&#xD;
          3. The patients who suffering from malignancy or a history of malignancy, a variety of&#xD;
             sexually transmitted diseases and HIV infection, tuberculosis infection, and other&#xD;
             condition which need to prohibit the use of immunosuppressive patients.&#xD;
&#xD;
          4. Be allergic to leflunomide, azathioprine&#xD;
&#xD;
          5. Pregnant or suckling period woman&#xD;
&#xD;
          6. Accompanied with mental disorders and have difficult to communication&#xD;
&#xD;
          7. Experienced myasthenia crisis in 3 months.&#xD;
&#xD;
          8. suffering from clear cardiopulmonary functional and brain abnormalities&#xD;
&#xD;
          9. Have a history of refractory hypertension or peptic ulcer .&#xD;
&#xD;
         10. One of the white blood cells, hemoglobin, and platelet count obvious abnormalities&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Weibin Liu, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affiliated Hospital, SUN YAT-SEN UNIVERSITY</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>April 6, 2022</last_update_submitted>
  <last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>First Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Liu Weibin</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>myasthenia gravis</keyword>
  <keyword>leflunomide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myasthenia Gravis</mesh_term>
    <mesh_term>Muscle Weakness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azathioprine</mesh_term>
    <mesh_term>Leflunomide</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/NCT01727193
org study id: ZS-LEF
nct id: NCT01727193
lead sponsor: 
has dmc: Yes
This is a randomized controlled clinical study. The investigators screen of eligible
      patients, randomized divide into the following two groups: corticosteroids + azathioprine
      group, corticosteroids + leflunomide group. The investigators treat the enrolled patients,
      estimate efficacy and observed the side effects according to the requirements of program. The
      investigators establish a clinical database for recording patients date and statistical
      analysis. Evaluation of short-term and long-term efficacy of thymectomized myasthenia gravis
      patients in the different group prove that what kind of treatment can improve the cure rate.
      The investigators will evaluate the acute toxicity (gastrointestinal side effects, liver and
      kidney dysfunction) and long-term toxicity (immune dysfunction, gonadal suppression) when the
      investigators apply these therapy in the treatment of different clinical types of myasthenia
      gravis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the percent of achieving good response
time frame: 144 weeks
description: Pharmacologic Remission (PR) was the primary efficacy endpoint observed. Record the time the patient appears from the time of medication to the time of PR, and calculate the percentage of PR patients in each arm. Criteria for PR: The patient has had no symptoms or signs of MG for at least 1 year and continues to take some form of therapy for MG. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted. Patients taking cholinesterase inhibitors are excluded from this category because their use suggests the presence of weakness.
measure: The changes of the disease severity and the antibody titer during the follow-up
time frame: 144 weeks
description: The magnitude by which QMG or ADL scores are reduced. Total amount of steroid used during the follow-up. Level of the acetylcholine receptor antibody.
arm group label: Azathioprine
arm group type: Active Comparator
description: cholinesterase inhibitors+Glucocorticoid +Azathioprine
arm group label: Leflunomide
arm group type: Active Comparator
description: cholinesterase inhibitors+glucocorticoid+Leflunomide
intervention type: Drug
intervention name: Azathioprine
description: The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 1 glucocorticoid + Azathioprine: Glucocorticoid (0.25mg/kg/d )plus Azathioprine at a starting dose of 50mg/d for 14 days, then increase up to 2mg/kg in 2 weeks.If no adverse events occurred , maintain the dose until 48 weeks.
arm group label: Azathioprine
intervention type: Drug
intervention name: Leflunomide
description: The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 2 glucocorticoid + Leflunomide: Glucocorticoid (0.25mg/kg/d )plus Leflunomide 20mg/d for adult, 10mg/d for child. if no adverse events occurred , maintain the dose until 48 weeks.
arm group label: Leflunomide
criteria: 
gender: All
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: No
last name: Weibin Liu, Doctor
role: Principal Investigator
affiliation: First Affiliated Hospital, Sun Yat-Sen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: First Affiliated Hospital, Sun Yat-Sen University
investigator full name: Liu Weibin
investigator title: Principal Investigator
mesh term: Myasthenia Gravis
mesh term: Muscle Weakness
mesh term: Azathioprine
mesh term: Leflunomide