<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/NCT03011268</url>
  </required_header>
  <id_info>
    <org_study_id>HMR2016-0.6</org_study_id>
    <secondary_id>2016-001409-18</secondary_id>
    <nct_id>NCT03011268</nct_id>
  </id_info>
  <brief_title>Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not?</brief_title>
  <acronym>BIOSTOP</acronym>
  <official_title>Continuing or Discontinuing Anti-tumor Necrosis Factor Treatment in Patients With Ulcerative Colitis in Clinical Remission: a Prospective Open Randomized Parallel-group Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Møre og Romsdal HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oslo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helse Møre og Romsdal HF</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The primary objective is to assess if discontinuation of anti- tumor necrosis factor alpha&#xD;
      (TNF) treatment in ulcerative colitis patients in sustained clinical remission, with the&#xD;
      option to restart treatment in the case of relapse, is non-inferior to continued anti-TNF&#xD;
      treatment. Secondary objectives are to assess the efficacy and safety of restarting anti-TNF&#xD;
      treatment after a relapse&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The BIOSTOP study is a prospective, open randomized, multicenter, parallel-group study to&#xD;
      compare clinical outcome of discontinuing (interventional group) compared to continuing&#xD;
      (control group) biologic treatment with anti-TNF in ulcerative colitis patients in clinical&#xD;
      remission.&#xD;
&#xD;
      Adult male and female patients with an established diagnosis of ulcerative colitis treated&#xD;
      for minimum one year with anti-TNF maintenance therapy and being in clinical remission during&#xD;
      the last 3 months are potential study patients. Eligible patients who have given their&#xD;
      informed written consent will be randomized 1:1 to either discontinue anti-TNF treatment or&#xD;
      to continue anti-TNF treatment for another two years.&#xD;
&#xD;
      Patients in the control group who are still in clinical and endoscopic remission after two&#xD;
      years on continued anti-TNF treatment, will then be switched to discontinue anti-TNF&#xD;
      treatment.&#xD;
&#xD;
      End of study/follow-up is after 4 years. In order to identify the primary endpoint&#xD;
      (occurrence of disease relapse), each study center will have a phone number for patients to&#xD;
      call in case of symptoms suspect of increased disease activity. If a patient is experiencing&#xD;
      a potential disease flare (6-point Mayo score &gt; 1) and/or 2 consecutive calprotectin tests&#xD;
      are positive (&gt; 200 mg/kg), an unscheduled visit including recto sigmoidoscopy will be&#xD;
      performed without delay to document disease status.&#xD;
&#xD;
      150 participants enrolled, September 2020 Covid 19 - randomization period extended until&#xD;
      31.12.2020&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 9, 2017</start_date>
  <completion_date type="Anticipated">February 1, 2025</completion_date>
  <primary_completion_date type="Actual">February 1, 2023</primary_completion_date>
  <phase>N/A</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>Proportion of patients in sustained clinical remission</measure>
    <time_frame>2 years</time_frame>
    <description>Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients in sustained clinical remission</measure>
    <time_frame>4 years</time_frame>
    <description>Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to relapse</measure>
    <time_frame>2 years</time_frame>
    <description>Relapse time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to relapse</measure>
    <time_frame>4 years</time_frame>
    <description>Relapse time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy</measure>
    <time_frame>2 years</time_frame>
    <description>Remission, but no need to restart anti-tnf therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy</measure>
    <time_frame>4 years</time_frame>
    <description>Remission, but no need to restart anti-tnf therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of relapse patients achieving remission after anti-TNF restart</measure>
    <time_frame>2 years</time_frame>
    <description>Remission after relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of relapse patients achieving remission after anti-TNF restart</measure>
    <time_frame>4 years</time_frame>
    <description>Remission after relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events and serious adverse events frequency and severity</measure>
    <time_frame>2 years</time_frame>
    <description>Adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events and serious adverse events frequency and severity</measure>
    <time_frame>4 years</time_frame>
    <description>Adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">174</enrollment>
  <condition>Colitis,Ulcerative</condition>
  <arm_group>
    <arm_group_label>Anti TNF discontinuation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Discontinuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anti TNF continuation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Discontinuation of anti-TNF treatment</intervention_name>
    <description>Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences</description>
    <arm_group_label>Anti TNF discontinuation</arm_group_label>
    <other_name>Remicade, Remsima, Inflectra, Humira, Simponi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Continuation of anti-TNF treatment</intervention_name>
    <description>Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue</description>
    <arm_group_label>Anti TNF continuation</arm_group_label>
    <other_name>Remicade, Remsima, Inflectra, Humira, Simponi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  confirmed diagnosis of ulcerative colitis&#xD;
&#xD;
          -  treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment&#xD;
&#xD;
          -  in sustained clinical remission during the last 3 months&#xD;
&#xD;
          -  capable of understanding and signing an informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Discontinuation of systemic 5-Aminosalicylic acid (ASA) or immunomodulatory therapy or&#xD;
             other medication that could affect disease activity during the last 3 months prior to&#xD;
             randomization&#xD;
&#xD;
          -  Any treatment of systemic corticosteroids due to disease exacerbation during the last&#xD;
             3 months (i.e. patients being in steroid free clinical remission)&#xD;
&#xD;
          -  Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory&#xD;
             therapy&#xD;
&#xD;
          -  Change in the anti-TNF treatment during the last 3 months due to disease related&#xD;
             factors, not including dose/frequency adjustments due to drug concentration&#xD;
             measurements&#xD;
&#xD;
          -  Use of any second-line anti-TNF medication irrespective of reason for stopping&#xD;
             first-line anti-TNF&#xD;
&#xD;
          -  Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration,&#xD;
             with the exception of discontinuation due to pregnancy&#xD;
&#xD;
          -  Detection of anti-TNF antibodies in moderate-high titers prior to randomization&#xD;
&#xD;
          -  Psychiatric or mental disorders&#xD;
&#xD;
          -  Alcohol abuse or other substance abuse&#xD;
&#xD;
          -  language barriers or other factors which makes adherence to the study protocol&#xD;
             impossible&#xD;
&#xD;
          -  Participation in any other studies&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  breastfeeding&#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>Dag Arne L Hoff, md, phd</last_name>
    <role>Study Director</role>
    <affiliation>Helse Møre og Romsdal Hospital Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helse Møre og Romsdal, Ålesund Sjukehus</name>
      <address>
        <city>Alesund</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haraldsplass Diakonale sykehus</name>
      <address>
        <city>Bergen</city>
        <zip>5009</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haukeland Universitetssykehus Helse Bergen HF</name>
      <address>
        <city>Bergen</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helse Førde, Førde Sentralsjukehus</name>
      <address>
        <city>Forde</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Østfold HF Kalnes</name>
      <address>
        <city>Fredrikstad</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Innlandet, Hamar Sykehus</name>
      <address>
        <city>Hamar</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitetssykehuset i Nord-Norge, Harstad</name>
      <address>
        <city>Harstad</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sørlandet Sykehus HF, Kristiansand</name>
      <address>
        <city>Kristiansand</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helse Møre og Romsdal, Kristiansund Sjukehus</name>
      <address>
        <city>Kristiansund</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helse Nord Trøndelag, Levanger Sykehus</name>
      <address>
        <city>Levanger</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akershus Universitetssykehus, Lørenskog</name>
      <address>
        <city>Lørenskog</city>
        <zip>1478</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo Universitetssykehus, Rikshospitalet</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo Universitetssykehus, Ullevål</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vestre Viken HF, Bærum Sykehus</name>
      <address>
        <city>Sandvika</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Telemark, Skien</name>
      <address>
        <city>Skien</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stavanger Universitetssykehus</name>
      <address>
        <city>Stavanger</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Vestfold, Tønsberg</name>
      <address>
        <city>Tonsberg</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helse Møre og Romsdal, Volda Sjukehus</name>
      <address>
        <city>Volda</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helse Bergen HF Voss Sjukehus</name>
      <address>
        <city>Voss</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>March 16, 2023</last_update_submitted>
  <last_update_submitted_qc>March 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors</keyword>
  <keyword>Infliximab</keyword>
  <keyword>Adalimumab</keyword>
  <keyword>Golimumab</keyword>
  <keyword>Recurrence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
    <mesh_term>Necrosis</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>Golimumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>At this time there is no such plan for IPD sharing. It might be an issue regarding material stored in the study Biobank - that will be elucidated at a later stage.</ipd_description>
  </patient_data>
  <!-- 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/NCT03011268
org study id: HMR2016-0.6
secondary id: 2016-001409-18
nct id: NCT03011268
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective is to assess if discontinuation of anti- tumor necrosis factor alpha
      (TNF) treatment in ulcerative colitis patients in sustained clinical remission, with the
      option to restart treatment in the case of relapse, is non-inferior to continued anti-TNF
      treatment. Secondary objectives are to assess the efficacy and safety of restarting anti-TNF
      treatment after a relapse
The BIOSTOP study is a prospective, open randomized, multicenter, parallel-group study to
      compare clinical outcome of discontinuing (interventional group) compared to continuing
      (control group) biologic treatment with anti-TNF in ulcerative colitis patients in clinical
      remission.

      Adult male and female patients with an established diagnosis of ulcerative colitis treated
      for minimum one year with anti-TNF maintenance therapy and being in clinical remission during
      the last 3 months are potential study patients. Eligible patients who have given their
      informed written consent will be randomized 1:1 to either discontinue anti-TNF treatment or
      to continue anti-TNF treatment for another two years.

      Patients in the control group who are still in clinical and endoscopic remission after two
      years on continued anti-TNF treatment, will then be switched to discontinue anti-TNF
      treatment.

      End of study/follow-up is after 4 years. In order to identify the primary endpoint
      (occurrence of disease relapse), each study center will have a phone number for patients to
      call in case of symptoms suspect of increased disease activity. If a patient is experiencing
      a potential disease flare (6-point Mayo score > 1) and/or 2 consecutive calprotectin tests
      are positive (> 200 mg/kg), an unscheduled visit including recto sigmoidoscopy will be
      performed without delay to document disease status.

      150 participants enrolled, September 2020 Covid 19 - randomization period extended until
      31.12.2020
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients in sustained clinical remission
time frame: 2 years
description: Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment
measure: Proportion of patients in sustained clinical remission
time frame: 4 years
description: Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment
measure: Time from randomization to relapse
time frame: 2 years
description: Relapse time
measure: Time from randomization to relapse
time frame: 4 years
description: Relapse time
measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
time frame: 2 years
description: Remission, but no need to restart anti-tnf therapy
measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
time frame: 4 years
description: Remission, but no need to restart anti-tnf therapy
measure: Proportion of relapse patients achieving remission after anti-TNF restart
time frame: 2 years
description: Remission after relapse
measure: Proportion of relapse patients achieving remission after anti-TNF restart
time frame: 4 years
description: Remission after relapse
measure: Adverse events and serious adverse events frequency and severity
time frame: 2 years
description: Adverse events
measure: Adverse events and serious adverse events frequency and severity
time frame: 4 years
description: Adverse events
arm group label: Anti TNF discontinuation
arm group type: Experimental
description: Discontinuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)
arm group label: Anti TNF continuation
arm group type: Active Comparator
description: Continuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)
intervention type: Other
intervention name: Discontinuation of anti-TNF treatment
description: Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences
arm group label: Anti TNF discontinuation
other name: Remicade, Remsima, Inflectra, Humira, Simponi
intervention type: Other
intervention name: Continuation of anti-TNF treatment
description: Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue
arm group label: Anti TNF continuation
other name: Remicade, Remsima, Inflectra, Humira, Simponi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dag Arne L Hoff, md, phd
role: Study Director
affiliation: Helse Møre og Romsdal Hospital Trust
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Norway
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Necrosis
mesh term: Adalimumab
mesh term: Infliximab
mesh term: Golimumab
mesh term: Antibodies, Monoclonal
sharing ipd: No
ipd description: At this time there is no such plan for IPD sharing. It might be an issue regarding material stored in the study Biobank - that will be elucidated at a later stage.