<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/NCT02994836</url>
  </required_header>
  <id_info>
    <org_study_id>GIS-SUSANTI-TNF-2015</org_study_id>
    <nct_id>NCT02994836</nct_id>
  </id_info>
  <brief_title>GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )</brief_title>
  <official_title>Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: Multicentre, Prospective, Randomized Clinical Trial and Economic Evaluation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación de Investigación Biomédica - Hospital Universitario de La Princesa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundación de Investigación Biomédica - Hospital Universitario de La Princesa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be a multicentre prospective randomized trial to assess the percentage of&#xD;
      patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission&#xD;
      at one year compared to those in which the treatment is continued at stable doses&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A multicentre prospective randomized trial.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      The discontinuation of anti-TNF treatment in inflammatory bowel disease (IBD) patients in&#xD;
      clinical remission is associated with an increased risk of recurrence compared with&#xD;
      maintaining such treatment.&#xD;
&#xD;
      Main objective:&#xD;
&#xD;
      To assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have&#xD;
      sustained clinical remission at one year compared to those in which the treatment is&#xD;
      continued at stable doses&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      To compare treatment discontinuation vs. treatment continuation of anti-TNF agents in&#xD;
      patients with Crohn´s disease or ulcerative colitis in terms of:&#xD;
&#xD;
        1. remission (relapse-free) time,&#xD;
&#xD;
        2. phenotype changes with both strategies&#xD;
&#xD;
        3. mucosal healing,&#xD;
&#xD;
        4. radiologic healing&#xD;
&#xD;
        5. impact on quality of life and productivity&#xD;
&#xD;
        6. safety&#xD;
&#xD;
        7. to identify relapse predictive factors.&#xD;
&#xD;
        8. To identify relapse predictive factors after anti-TNF drug discontinuation&#xD;
&#xD;
        9. Determining the profile of serum cytokines in patients with both strategies, depending&#xD;
           on drug exposure and if maintained clinical remission or relapse.&#xD;
&#xD;
      Planned number of subject to be included: 194&#xD;
&#xD;
      The participation of at 50 hospitals in Spain with an inclusion of about 5 patients per&#xD;
      hospital is required..&#xD;
&#xD;
      Case report Form was designed on REDCap (a free, secure, web-based application designed to&#xD;
      support data capture for research studies).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 21, 2017</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sustained clinical remission after one year of follow-up (after discontinuing or continuing treatment with anti-TNF).</measure>
    <time_frame>Change at 12 months.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical activity assessment</measure>
    <time_frame>Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12</time_frame>
    <description>On Crohn´s Disease: Measure by Crohn´s Disease Activity Index (CDAI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endoscopic activity assessment</measure>
    <time_frame>12 Months. On the Month 0, month 12 or relapse</time_frame>
    <description>On Crohn´s Disease: Measure by Simplified endoscopic activity score for Crohn´s disease (SES-CD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiologic activity assessment</measure>
    <time_frame>12 Months. Month 0, month 12 or relapse</time_frame>
    <description>Measure by absence of contrast enhancement, edema or presence of ulcers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessment</measure>
    <time_frame>Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12</time_frame>
    <description>Measure by the Inflammatory Bowel Disease Questionnaire (IBDQ-9)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Work productivity and activity assessment</measure>
    <time_frame>Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12</time_frame>
    <description>Measure by &quot;Spanish Work Productivity and Activity Impairment Questionnaire&quot;.This questionnaire assessments the sum of work time missed because IBD and impairment while working yields the overall work impairment (productivity loss) score. Scores are expressed as percentages of impairment/productivity loss, with higher scores indicating greater impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical activity assessment</measure>
    <time_frame>Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12</time_frame>
    <description>On the Ulcerative Colitis disease: Measure by Mayo Scoring System</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endoscopic activity assessment</measure>
    <time_frame>12 Months. On the Month 0, month 12 or relapse</time_frame>
    <description>On the Ulcerative Colitis disease: Measure by Mayo endoscopic score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">139</enrollment>
  <condition>Crohn's Disease</condition>
  <condition>Inflammatory Bowel Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Anti-TNF</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) or Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anti-TNF discontinuation (Placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Physiological saline solution (Infusion-Intravenous use) or Physiological saline solution (Injection-subcutaneous use)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-TNF: Infliximab (Infusion)</intervention_name>
    <description>Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)</description>
    <arm_group_label>Anti-TNF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-TNF discontinuation: Physiological saline solution</intervention_name>
    <description>Physiological saline solution (Infusion-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)</description>
    <arm_group_label>Anti-TNF discontinuation (Placebo)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-TNF:Adalimumab (Subcutaneus)</intervention_name>
    <description>Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).</description>
    <arm_group_label>Anti-TNF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-TNF discontinuation: Physiological saline solution</intervention_name>
    <description>Physiological saline solution (Injection-subcutaneous use)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).</description>
    <arm_group_label>Anti-TNF discontinuation (Placebo)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with IBD by the usual criteria; both Crohn's and ulcerative colitis&#xD;
             disease.&#xD;
&#xD;
          -  Patients older than 18 years.&#xD;
&#xD;
          -  In the case of patients with Crohn's disease the indication treatment with anti-TNF it&#xD;
             must have been for luminal involvement (no perianal).&#xD;
&#xD;
          -  Are currently in clinical remission.&#xD;
&#xD;
          -  The clinical remission period with the drug at non-intensified dose it must have been&#xD;
             at least 6 months.&#xD;
&#xD;
        The administration of ≥10 mg/kg/8 weeks or 5 mg / kg / ≤ 4 weeks, in the case of&#xD;
        infliximab, and 40 mg / week, in the case of adalimumab, is considered an intensified dose.&#xD;
&#xD;
          -  At the time of inclusion, the patient should be receiving concomitant&#xD;
             immunosuppressants (thiopurine or methotrexate) to anti-TNF treatment, and must have&#xD;
             received these immunosuppressive drugs at stable doses for at least the last 3 months.&#xD;
&#xD;
          -  In patients with Crohn's disease or ulcerative colitis disease, at baseline&#xD;
             colonoscopy (made up to 3 months prior to the screening visit) should not be&#xD;
             &quot;significant&quot; injuries.&#xD;
&#xD;
          -  In the case of patients with Crohn's ileal or ileocolic disease, in magnetic resonance&#xD;
             whole should not be &quot;significant&quot; injuries.(made up to 3 months prior to the screening&#xD;
             visit)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years.&#xD;
&#xD;
          -  Patients who have been treated with anti-TNF for other indication than the IBD.&#xD;
&#xD;
          -  Patients with Crohn's disease in which the indication for treatment with anti-TNF has&#xD;
             been the perianal involvement (or luminal and perianal both); or showing active&#xD;
             perianal disease at the time of inclusion.&#xD;
&#xD;
          -  Patients who are not receiving concomitant treatment with immunosuppressants&#xD;
             (thiopurine or methotrexate) at the moment (and in the previous 3 months).&#xD;
&#xD;
          -  Patients undergoing bowel resection surgery; therefore, patients who began anti-TNF&#xD;
             therapy to prevent or treat postoperative recurrence in Crohn's disease will be&#xD;
             excluded.&#xD;
&#xD;
          -  Presence of &quot;significant&quot; endoscopic or radiological lesions&#xD;
&#xD;
          -  Advanced chronic illness or any other condition that prevents the patient from coming&#xD;
             to the clinic for monitoring or follow-up.&#xD;
&#xD;
          -  Patients who are pregnant, breastfeeding or intending to become pregnant during the&#xD;
             course of the study.&#xD;
&#xD;
          -  Refusal to give consent for participation in the study.&#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>Javier MD Perez Gisbert, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundación de Investigación Biomédica - Hospital Universitario de La Princesa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario de La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
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  <verification_date>February 2023</verification_date>
  <study_first_submitted>October 24, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's Disease</keyword>
  <keyword>Inflammatory bowel disease</keyword>
  <keyword>Anti-TNF discontinuation</keyword>
  <keyword>Ulcerative colitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Pharmaceutical Solutions</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/NCT02994836
org study id: GIS-SUSANTI-TNF-2015
nct id: NCT02994836
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will be a multicentre prospective randomized trial to assess the percentage of
      patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission
      at one year compared to those in which the treatment is continued at stable doses
A multicentre prospective randomized trial.

      Hypothesis:

      The discontinuation of anti-TNF treatment in inflammatory bowel disease (IBD) patients in
      clinical remission is associated with an increased risk of recurrence compared with
      maintaining such treatment.

      Main objective:

      To assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have
      sustained clinical remission at one year compared to those in which the treatment is
      continued at stable doses

      Secondary objectives:

      To compare treatment discontinuation vs. treatment continuation of anti-TNF agents in
      patients with Crohn´s disease or ulcerative colitis in terms of:

        1. remission (relapse-free) time,

        2. phenotype changes with both strategies

        3. mucosal healing,

        4. radiologic healing

        5. impact on quality of life and productivity

        6. safety

        7. to identify relapse predictive factors.

        8. To identify relapse predictive factors after anti-TNF drug discontinuation

        9. Determining the profile of serum cytokines in patients with both strategies, depending
           on drug exposure and if maintained clinical remission or relapse.

      Planned number of subject to be included: 194

      The participation of at 50 hospitals in Spain with an inclusion of about 5 patients per
      hospital is required..

      Case report Form was designed on REDCap (a free, secure, web-based application designed to
      support data capture for research studies).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Sustained clinical remission after one year of follow-up (after discontinuing or continuing treatment with anti-TNF).
time frame: Change at 12 months.
measure: Clinical activity assessment
time frame: Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12
description: On Crohn´s Disease: Measure by Crohn´s Disease Activity Index (CDAI)
measure: Endoscopic activity assessment
time frame: 12 Months. On the Month 0, month 12 or relapse
description: On Crohn´s Disease: Measure by Simplified endoscopic activity score for Crohn´s disease (SES-CD).
measure: Radiologic activity assessment
time frame: 12 Months. Month 0, month 12 or relapse
description: Measure by absence of contrast enhancement, edema or presence of ulcers
measure: Quality of life assessment
time frame: Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12
description: Measure by the Inflammatory Bowel Disease Questionnaire (IBDQ-9)
measure: The Work productivity and activity assessment
time frame: Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12
description: Measure by "Spanish Work Productivity and Activity Impairment Questionnaire".This questionnaire assessments the sum of work time missed because IBD and impairment while working yields the overall work impairment (productivity loss) score. Scores are expressed as percentages of impairment/productivity loss, with higher scores indicating greater impairment.
measure: Clinical activity assessment
time frame: Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12
description: On the Ulcerative Colitis disease: Measure by Mayo Scoring System
measure: Endoscopic activity assessment
time frame: 12 Months. On the Month 0, month 12 or relapse
description: On the Ulcerative Colitis disease: Measure by Mayo endoscopic score.
arm group label: Anti-TNF
arm group type: Active Comparator
description: Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) or Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)
arm group label: Anti-TNF discontinuation (Placebo)
arm group type: Placebo Comparator
description: Physiological saline solution (Infusion-Intravenous use) or Physiological saline solution (Injection-subcutaneous use)
intervention type: Biological
intervention name: Anti-TNF: Infliximab (Infusion)
description: Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)
arm group label: Anti-TNF
intervention type: Drug
intervention name: Anti-TNF discontinuation: Physiological saline solution
description: Physiological saline solution (Infusion-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)
arm group label: Anti-TNF discontinuation (Placebo)
intervention type: Biological
intervention name: Anti-TNF:Adalimumab (Subcutaneus)
description: Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).
arm group label: Anti-TNF
intervention type: Drug
intervention name: Anti-TNF discontinuation: Physiological saline solution
description: Physiological saline solution (Injection-subcutaneous use)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).
arm group label: Anti-TNF discontinuation (Placebo)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Javier MD Perez Gisbert, PhD
role: Principal Investigator
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
facility: 
country: Spain
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responsible party type: Sponsor
mesh term: Crohn Disease
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
mesh term: Adalimumab
mesh term: Infliximab
mesh term: Pharmaceutical Solutions