<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/NCT02247258</url>
  </required_header>
  <id_info>
    <org_study_id>ML3121</org_study_id>
    <nct_id>NCT02247258</nct_id>
  </id_info>
  <brief_title>Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence.</brief_title>
  <official_title>Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence: Systematic Versus Endoscopic-directed Treatment. A Multi-center, Randomized, Clinical Practice Evaluation Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>International organization for the study of inflammatory bowel disease (IOIBD)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate if in the prevention of postoperative recurrence&#xD;
      of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to&#xD;
      delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by&#xD;
      endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and&#xD;
      surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow recruitment&#xD;
  </why_stopped>
  <start_date>October 2005</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endoscopic remission</measure>
    <time_frame>Week 102</time_frame>
    <description>The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete endoscopic remission</measure>
    <time_frame>Week 102</time_frame>
    <description>The percentage of patients with a Rutgeerts' score of i0 at 102 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absence of endoscopic relapse</measure>
    <time_frame>Week 102</time_frame>
    <description>The percentage of patients with a Rutgeerts' score of i0-i2 at 102 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical remission</measure>
    <time_frame>Week 102</time_frame>
    <description>The percentage of patients in clinical remission (Crohn's disease activity index, CDAI &lt;150) at 102 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sustained clinical remission</measure>
    <time_frame>Week 102</time_frame>
    <description>Crohn's disease activity index, CDAI &lt; 150 throughout the 102 weeks study period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological remission</measure>
    <time_frame>Week 102</time_frame>
    <description>The percentage of patients with radiological remission at 102 weeks.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Crohn Disease</condition>
  <condition>Recurrence</condition>
  <condition>Azathioprine</condition>
  <condition>Prevention</condition>
  <arm_group>
    <arm_group_label>Systematic azathioprine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Endoscopy-driven azathioprine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azathioprine</intervention_name>
    <description>See arm/group descriptions</description>
    <arm_group_label>Systematic azathioprine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azathioprine in case of endoscopic recurrence</intervention_name>
    <description>See arm/group descriptions</description>
    <arm_group_label>Endoscopy-driven azathioprine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ileocolonoscopy</intervention_name>
    <description>See arm/group descriptions</description>
    <arm_group_label>Endoscopy-driven azathioprine group</arm_group_label>
    <arm_group_label>Systematic azathioprine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Small bowel follow trough</intervention_name>
    <description>See arm/group descriptions</description>
    <arm_group_label>Endoscopy-driven azathioprine group</arm_group_label>
    <arm_group_label>Systematic azathioprine group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Scheduled surgery for Crohn's disease (CD) with ileocolonic resection. Diagnosis of CD&#xD;
             confirmed at least 4 months prior to surgery based on radiology and/or endoscopy.&#xD;
&#xD;
          2. Having an increased risk for postoperative relapse for any of the following reasons:&#xD;
             (1) active inflammatory disease with C-reactive protein level (CRP) elevated above 10&#xD;
             mg/L, or the use of antibiotics, steroids or biological therapy including infliximab&#xD;
             for active ileal disease within 2 months before surgery which were administered for&#xD;
             Crohn's disease and not for another unrelated intercurrent inflammatory or infectious&#xD;
             disease; (2) perforating disease defined as the presence of entero-enteric or&#xD;
             enterocutaneous fistulas or perivisceral abscess formation within 2 months before&#xD;
             surgery. Perianal fistulizing disease will not be considered as an indication of&#xD;
             perforating disease in the ileum or right-sided colon. (3) Previous ileo-colonic&#xD;
             resection, (4) active smoking, (5) age below 30.&#xD;
&#xD;
          3. Males and females 16-75 years old.&#xD;
&#xD;
          4. Curative surgical resection. All macroscopically inflamed colonic segments (except for&#xD;
             anorectal involvement) are to be removed at surgery. Stricturoplasties in small bowel&#xD;
             segments not involving the anastomotic region are allowed.&#xD;
&#xD;
          5. Patients able to start oral nutrition and oral therapy within 14 days from surgery.&#xD;
&#xD;
          6. Patients able and willing to give written informed consent&#xD;
&#xD;
          7. Women of childbearing potential should have a negative pregnancy test at inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who only had strictureplasties or ileal/colonic resection without a new&#xD;
             ileo-colonic anastomosis. Patients with ileorectal anastomosis.&#xD;
&#xD;
          2. Patients with no increased risk of postoperative relapse as defined before.&#xD;
&#xD;
          3. Patients with a known intolerance to azathioprine/6-mercaptopurine or with known&#xD;
             homozygous thiopurine methyltransferase-low mutation.&#xD;
&#xD;
          4. Patients in whom more than 100 cm of small bowel has been previously resected.&#xD;
&#xD;
          5. Patients with active perianal disease or colorectal stenosis precluding&#xD;
             ileocolonoscopy&#xD;
&#xD;
          6. Patients with sepsis or other postoperative complications necessitating use of&#xD;
             antibiotics for more than 14 days after surgery.&#xD;
&#xD;
          7. Patients with liver test abnormalities (serum glutamate oxaloacetate transaminase,&#xD;
             serum glutamate pyruvate transaminase, alkaline phosphatase, bilirubin &gt; 2 ULN),&#xD;
             leucopenia (&lt;3000 white blood cell count /µL, &lt;1500 neutrophils /µL), thrombopenia&#xD;
             with &lt; 50.000 platelets/mm3.&#xD;
&#xD;
          8. Patients with severe renal, pulmonary or cardiac disease.&#xD;
&#xD;
          9. Pregnant or lactating women.&#xD;
&#xD;
         10. Ongoing alcohol or substance abuse.&#xD;
&#xD;
         11. Ongoing or recent (within 6 months) infectious disease (viral hepatitis, tuberculosis,&#xD;
             AIDS, Herpes zoster related disease).&#xD;
&#xD;
         12. Known malignancy 5 years from surgery except for superficial epithelioma of the skin&#xD;
             with curative resection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gert Van Assche, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Imelda Ziekenhuis</name>
      <address>
        <city>Bonheiden</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univerzity Karlovy</name>
      <address>
        <city>Prague</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evangelismos Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czech Republic</country>
    <country>Greece</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <last_update_submitted>May 28, 2015</last_update_submitted>
  <last_update_submitted_qc>May 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azathioprine</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/NCT02247258
org study id: ML3121
nct id: NCT02247258
lead sponsor: 
collaborator: 
has dmc: No
The objective of this study is to evaluate if in the prevention of postoperative recurrence
      of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to
      delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by
      endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and
      surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Endoscopic remission
time frame: Week 102
description: The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks
measure: Complete endoscopic remission
time frame: Week 102
description: The percentage of patients with a Rutgeerts' score of i0 at 102 weeks
measure: Absence of endoscopic relapse
time frame: Week 102
description: The percentage of patients with a Rutgeerts' score of i0-i2 at 102 weeks
measure: Clinical remission
time frame: Week 102
description: The percentage of patients in clinical remission (Crohn's disease activity index, CDAI <150) at 102 weeks
measure: Sustained clinical remission
time frame: Week 102
description: Crohn's disease activity index, CDAI < 150 throughout the 102 weeks study period
measure: Radiological remission
time frame: Week 102
description: The percentage of patients with radiological remission at 102 weeks.
arm group label: Systematic azathioprine group
arm group type: Active Comparator
description: Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.
arm group label: Endoscopy-driven azathioprine group
arm group type: Active Comparator
description: Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.
intervention type: Drug
intervention name: Azathioprine
description: See arm/group descriptions
arm group label: Systematic azathioprine group
intervention type: Drug
intervention name: Azathioprine in case of endoscopic recurrence
description: See arm/group descriptions
arm group label: Endoscopy-driven azathioprine group
intervention type: Procedure
intervention name: Ileocolonoscopy
description: See arm/group descriptions
arm group label: Endoscopy-driven azathioprine group
arm group label: Systematic azathioprine group
intervention type: Procedure
intervention name: Small bowel follow trough
description: See arm/group descriptions
arm group label: Endoscopy-driven azathioprine group
arm group label: Systematic azathioprine group
criteria: 
gender: All
minimum age: 16 Years
maximum age: 75 Years
healthy volunteers: No
last name: Gert Van Assche, MD PhD
role: Principal Investigator
affiliation: UZ Leuven
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Czech Republic
country: Greece
responsible party type: Sponsor
mesh term: Crohn Disease
mesh term: Recurrence
mesh term: Azathioprine