<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/NCT03043846</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A00564-47</org_study_id>
    <nct_id>NCT03043846</nct_id>
  </id_info>
  <brief_title>Treat to Target Trial in Axial Spondylo Arthritis : The TICOSPA (Tight Control in Spondyloarthritis)</brief_title>
  <acronym>TICOSPA</acronym>
  <official_title>Treat to Target Trial in Axial Spondylo Arthritis : The TICOSPA (Tight Control in Spondyloarthritis)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Association de Recherche Clinique en Rhumatologie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>RCTs</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Association de Recherche Clinique en Rhumatologie</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 is a not interventional, pragmatic, prospective, randomized (cluster) study to evaluate&#xD;
      the potential benefit of a Treat to Target approach in comparison to routine treatment (i.e.&#xD;
      usual care) in patients with axial spondyloarthritis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is reflecting the usual care either in accordance to the treating rheumatologist&#xD;
      (arm: usual care) or in accordance to the international scientific recommendations (arm: T2T)&#xD;
&#xD;
      The tight control means that as soon as a treatment is initiated in a patient, the time&#xD;
      permitting to evaluate its potential efficacy/safety has to be determined. In terms of&#xD;
      safety, such time frame can be very short based on the occurrence of adverse events. In terms&#xD;
      of efficacy it is usually recommended to evaluate an NSAIDs after 2 to 4 weeks of treatment&#xD;
      intake and the TNF blockers after 12 to 16 weeks.&#xD;
&#xD;
      The Treat to Target means that there is an a priori decision of the target to reach while&#xD;
      initiating a treatment and more importantly an a priori decision to intensify the treatment&#xD;
      in case such target is not achieved.&#xD;
&#xD;
      There will be 2 arms in the study (tight control and treat to target arm and usual care arm).&#xD;
&#xD;
      160 patients (80 patients per arm) will be included during one year by 18 centers (10 in&#xD;
      France, 4 in Belgium and 4 in Netherlands). Patients will be followed during 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2016</start_date>
  <completion_date type="Actual">June 18, 2019</completion_date>
  <primary_completion_date type="Actual">June 18, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To compare the changes in ASASHI-NRS over the one year of follow-up in the 2 groups</measure>
    <time_frame>After a one year follow-up</time_frame>
    <description>In the original protocol, the main objective was &quot;to compare the percentage of patients with a significant improvement in the ASAS-HI score after a one year follow-up in the 2 groups&quot;.&#xD;
However, after further research on the methodology to better assess the treatment effect on a pragmatic cluster-based strategy trial, we propose to change the primary objective for two reasons in order to:&#xD;
Calculate a &quot;significant improvement&quot; of the ASAS-HI, we would need to be aware of the minimally clinically important difference, and this threshold has not been yet defined for the regular ASAS-HI nor for the ASAS-HI NRS.&#xD;
Account for the reduced heterogeneity induced by the fact that patients are clustered, a multilevel analysis (e.g. mixed models with two random effects, the subject and the cluster or center) has been proposed as the most appropriate method.&#xD;
Therefore, we have amended the main objective to: &quot;To compare the changes in ASASHI-NRS over the one year of follow-up in the 2 groups&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare the percentage of patients reaching an ASDAS major improvement after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the percentage of patients reaching an ASDAS clinically important improvement after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the percentage of patients reaching a BASDAI 50 after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the change in the ASDAS over one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the change in the BASDAI over one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the change in the ASAS-NSAID score over one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the WPAI after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the EQ5D after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the self-report questionnaire on health resource utilization after a one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the number and type of adverse events occuring over one year follow-up in the 2 groups.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the treatment effect (...) within the T2T depending on the compliance to the T2T treatment.</measure>
    <time_frame>After a one year follow-up</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">163</enrollment>
  <condition>Axial Spondyloarthritis</condition>
  <arm_group>
    <arm_group_label>Tight control and Treat to Target arm</arm_group_label>
    <description>For this group, the treating rheumatologist will agree to monitor very closely (at least every 4 weeks) and also to treat their patients in accordance with a pre-defined strategy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care arm</arm_group_label>
    <description>For this arm, the treating rheumatologists will continue to manage the enrolled patients in accordance to their usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Follow-up every 3 months during 1 year (data collection in eCRF)</intervention_name>
    <arm_group_label>Tight control and Treat to Target arm</arm_group_label>
    <arm_group_label>Usual care arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Follow-up every month to follow the pre-defined strategy</intervention_name>
    <arm_group_label>Tight control and Treat to Target arm</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with a diagnosis of predominant axial spondyloarthritis according to the axial ASAS&#xD;
        criteria AND the opinion of the treating rheumatologist, and an active disease defined as&#xD;
        an (ASDAS ≥ 2.1), and non-optimally treated with NSAIDs.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (between 18 and 65 years old)&#xD;
&#xD;
          -  With a diagnosis of axial spondyloarthritis according to the axial ASAS criteria AND&#xD;
             the opinion of the treating rheumatologist.&#xD;
&#xD;
          -  Active disease defined as an ASDAS ≥ 2.1&#xD;
&#xD;
          -  Predominant axial disease meaning that:&#xD;
&#xD;
               -  Patients with non-spinal rheumatological symptoms and/or extra-rheumatological&#xD;
                  manifestations requiring at baseline the initiation of a specific treatment will&#xD;
                  be excluded.&#xD;
&#xD;
               -  Patients with a past history and/or a current well controlled non-spinal&#xD;
                  rheumatological or extra-rheumatological features will be eligible for the study.&#xD;
&#xD;
          -  Non-optimally treated with NSAIDs (i.e. who have not received at least 2 NSAIDS, daily&#xD;
             during at least 2 weeks at full dose, during the last year). Annex II summarizes the&#xD;
             list of commonly used NSAIDs and the definition of a &quot;full&quot; use.&#xD;
&#xD;
          -  With available pelvic X-rays, B27 and MRI of the sacro-iliac joints (performed at any&#xD;
             time since symptoms onset)&#xD;
&#xD;
          -  With no contraindication to the use of a NSAID&#xD;
&#xD;
          -  With no intake of apremilast during the previous 3 months&#xD;
&#xD;
          -  Able to understand the objectives of the study and to fill the questionnaires&#xD;
&#xD;
          -  Written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UZ GENT</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reumatologie Medizorg</name>
      <address>
        <city>Merksem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Alma</name>
      <address>
        <city>Sijsele</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Gabriel Montpied</name>
      <address>
        <city>Clermont-ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Le Mans</name>
      <address>
        <city>Le Mans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Lapeyronnie</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ch Mulhouse</name>
      <address>
        <city>Mulhouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de La Pitie Salpetriere</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Henri Mondor</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Rouen</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Toulouse</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCG</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuyderland MC</name>
      <address>
        <city>Heerlen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LUMC</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maastricht UMC</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>September 26, 2019</last_update_submitted>
  <last_update_submitted_qc>September 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Treat to Target approach</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Axial Spondyloarthritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03043846
org study id: 2016-A00564-47
nct id: NCT03043846
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a not interventional, pragmatic, prospective, randomized (cluster) study to evaluate
      the potential benefit of a Treat to Target approach in comparison to routine treatment (i.e.
      usual care) in patients with axial spondyloarthritis.
This study is reflecting the usual care either in accordance to the treating rheumatologist
      (arm: usual care) or in accordance to the international scientific recommendations (arm: T2T)

      The tight control means that as soon as a treatment is initiated in a patient, the time
      permitting to evaluate its potential efficacy/safety has to be determined. In terms of
      safety, such time frame can be very short based on the occurrence of adverse events. In terms
      of efficacy it is usually recommended to evaluate an NSAIDs after 2 to 4 weeks of treatment
      intake and the TNF blockers after 12 to 16 weeks.

      The Treat to Target means that there is an a priori decision of the target to reach while
      initiating a treatment and more importantly an a priori decision to intensify the treatment
      in case such target is not achieved.

      There will be 2 arms in the study (tight control and treat to target arm and usual care arm).

      160 patients (80 patients per arm) will be included during one year by 18 centers (10 in
      France, 4 in Belgium and 4 in Netherlands). Patients will be followed during 1 year.
observational model: Cohort
time perspective: Prospective
measure: To compare the changes in ASASHI-NRS over the one year of follow-up in the 2 groups
time frame: After a one year follow-up
description: In the original protocol, the main objective was "to compare the percentage of patients with a significant improvement in the ASAS-HI score after a one year follow-up in the 2 groups".
However, after further research on the methodology to better assess the treatment effect on a pragmatic cluster-based strategy trial, we propose to change the primary objective for two reasons in order to:
Calculate a "significant improvement" of the ASAS-HI, we would need to be aware of the minimally clinically important difference, and this threshold has not been yet defined for the regular ASAS-HI nor for the ASAS-HI NRS.
Account for the reduced heterogeneity induced by the fact that patients are clustered, a multilevel analysis (e.g. mixed models with two random effects, the subject and the cluster or center) has been proposed as the most appropriate method.
Therefore, we have amended the main objective to: "To compare the changes in ASASHI-NRS over the one year of follow-up in the 2 groups".
measure: To compare the percentage of patients reaching an ASDAS major improvement after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the percentage of patients reaching an ASDAS clinically important improvement after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the percentage of patients reaching a BASDAI 50 after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the change in the ASDAS over one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the change in the BASDAI over one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the change in the ASAS-NSAID score over one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the WPAI after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the EQ5D after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the self-report questionnaire on health resource utilization after a one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the number and type of adverse events occuring over one year follow-up in the 2 groups.
time frame: After a one year follow-up
measure: To compare the treatment effect (...) within the T2T depending on the compliance to the T2T treatment.
time frame: After a one year follow-up
arm group label: Tight control and Treat to Target arm
description: For this group, the treating rheumatologist will agree to monitor very closely (at least every 4 weeks) and also to treat their patients in accordance with a pre-defined strategy.
arm group label: Usual care arm
description: For this arm, the treating rheumatologists will continue to manage the enrolled patients in accordance to their usual care.
intervention type: Other
intervention name: Follow-up every 3 months during 1 year (data collection in eCRF)
arm group label: Tight control and Treat to Target arm
arm group label: Usual care arm
intervention type: Other
intervention name: Follow-up every month to follow the pre-defined strategy
arm group label: Tight control and Treat to Target arm
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: Netherlands
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Axial Spondyloarthritis
sharing ipd: No