<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/NCT02997605</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/15/7824</org_study_id>
    <secondary_id>2016-001618-18</secondary_id>
    <secondary_id>PHRC</secondary_id>
    <nct_id>NCT02997605</nct_id>
  </id_info>
  <brief_title>Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients</brief_title>
  <acronym>STAR</acronym>
  <official_title>Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients in Low Disease Activity or Remission.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</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>
      The purpose of this study is to compare the proportion of patients who could withdraw from&#xD;
      prednisone and hydrocortisone one year after a progressive decrease of GC (GC tapering) or a&#xD;
      hydrocortisone replacement therapy in rheumatoid arthritis in remission or low disease&#xD;
      activity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      French multicenter double-blind controlled parallel-group randomized clinical trial Phase IV&#xD;
      assessing whether a hydrocortisone replacement therapy could increase the success rate of GC&#xD;
      withdrawal at one year, in patients with Rheumatoid Arthritis in low disease activity or&#xD;
      remission, in comparison to progressive decrease of GC (GC tapering).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">January 27, 2022</completion_date>
  <primary_completion_date type="Actual">January 27, 2022</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>proportion of patients who could withdraw from prednisone and hydrocortisone at one year</measure>
    <time_frame>one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement</time_frame>
    <description>To compare a prednisone tapering strategy to a hydrocortisone replacement strategy on the success rate of prednisone and hydrocortisone withdrawal at one year in Rheumatoid Arthritis patients in low disease activity or remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>proportion of patients who could withdraw from prednisone</measure>
    <time_frame>one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement</time_frame>
    <description>To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with acute adrenal insufficiency</measure>
    <time_frame>one year</time_frame>
    <description>To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with biological adrenal insufficiency</measure>
    <time_frame>one year</time_frame>
    <description>To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients needing extra prednisone to control flares</measure>
    <time_frame>one year</time_frame>
    <description>To compare the proportion of patients needing extra prednisone to control flares</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients who have at least one flare confirmed by the investigator during the protocol.</measure>
    <time_frame>one year</time_frame>
    <description>To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis)</measure>
    <time_frame>one year</time_frame>
    <description>To compare the area under the curve of the means of the FLARE (Flare Assessment in Rheumatoid Arthritis) at one year with a self-assessment questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients in DAS28 remission and in DAS28 low disease activity</measure>
    <time_frame>7 and 12 months</time_frame>
    <description>To compare the proportion of patients in DAS28 remission and in DAS28 low disease activity at 7 and 12 months between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medians of Health Assessment Questionnaire (HAQ)</measure>
    <time_frame>4, 7 months and 1 year</time_frame>
    <description>To compare the medians of HAQ at 4, 7 months and one year between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medians of Rheumatoid Arthritis Impact of Disease (RAID)</measure>
    <time_frame>4, 7 months and 1 year</time_frame>
    <description>To compare the medians of RAID at 4, 7 months and one year between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medians of EuroQol 5-dimensional Descriptive system (EQ-5D)</measure>
    <time_frame>4, 7 months and 1 year</time_frame>
    <description>To compare the medians of EQ-5D at 4, 7 months and one year between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F)</measure>
    <time_frame>4, 7 months and 1 year</time_frame>
    <description>To compare the medians of FACIT-F at 4, 7 months and one year between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with Serious Adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>To compare the proportion of patients with Serious Adverse events at one year between the groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>RheumatoId Arthritis</condition>
  <arm_group>
    <arm_group_label>Glucocorticoid (GC) tapering</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>&quot;GC tapering group&quot;: patients will be asked to taper prednisone taken every morning at 8.00 AM by decreasing the daily dose by 1 mg every month as soon as they are in remission or Low Disease Activity (LDA). In addition they will receive a placebo of 20 mg/day of hydrocortisone (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg/day (at 8.00 AM) of hydrocortisone placebo for 3 months before discontinuing the hydrocortisone placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydrocortisone replacer</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>&quot;Hydrocortisone replacer group&quot;: patients will replace prednisone with 20 mg of hydrocortisone on a daily basis (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg daily (at 8.00 AM) for 3 months then stop as soon as they are in remission or LDA, as well as a prednisone placebo (at 8.00 AM) with a schedule to taper the prednisone placebo by 1mg/day every month until discontinuation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GlucoCorticoid</intervention_name>
    <description>After inclusion in the study, the first part is an open follow-up period where all patients will receive 5 mg of prednisone daily for one month. After one month, if patients still have a DAS28 ≤3.2, they will be randomized into two arms: Group 1: &quot;GC tapering group&quot; / Group 2: &quot;Hydrocortisone replacement group&quot;.&#xD;
After randomisation, there are four scheduled visits: M4, M7, M9 and M12. Patients withdrawing from GC therapy will be instructed, that if they start feeling unwell during or after the GC tapering protocol they should not taper the steroid dose any further, but contact the centre responsible for the protocol. If GC induced adrenal insufficiency is confirmed or strongly suspected, GC replacement will be secured using hydrocortisone.</description>
    <arm_group_label>Glucocorticoid (GC) tapering</arm_group_label>
    <arm_group_label>Hydrocortisone replacer</arm_group_label>
    <other_name>Prednisone, Hydrocortisone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥ 18 years old.&#xD;
&#xD;
          -  Fulfilling the 2010 American College of Rheumatology (ACR)/EULAR criteria for RA.&#xD;
&#xD;
          -  Treated with a stable dose of Synthetic Disease Modifying Anti-Rheumatic Drugs&#xD;
             (sDMARD) or Biological Disease Modifying Anti-Rheumatic Drug (bDMARD) for at least 3&#xD;
             months.&#xD;
&#xD;
          -  Who have been treated with prednisone or prednisolone for at least 6 months.&#xD;
&#xD;
          -  With a stable dose of prednisone or prednisolone of 5mg/day for at least 3 months.&#xD;
&#xD;
          -  With a DAS28 ≤3.2 for at least 3 months.&#xD;
&#xD;
          -  Patients with health insurance&#xD;
&#xD;
          -  Patients who have signed a written informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any chronic condition that would need long term corticoid use (e.g. chronic lung&#xD;
             diseases).&#xD;
&#xD;
          -  Evidence of a flare within the last 3 months.&#xD;
&#xD;
          -  Evidence of an allergy or intolerance to hydrocortisone or prednisone.&#xD;
&#xD;
          -  Chronic idiopathic, or autoimmune clinical adrenal insufficiency.&#xD;
&#xD;
          -  GC joint injections within the last 3 months or scheduled in the next 3 months.&#xD;
&#xD;
          -  Any GC intake expected more than &gt;5mg/day within the next 12 months.&#xD;
&#xD;
          -  Association with sultopride and with live vaccines&#xD;
&#xD;
          -  Significant trauma or major surgery within the 3 months prior to the baseline visit.&#xD;
&#xD;
          -  Scheduled surgery in the next 12 months.&#xD;
&#xD;
          -  Fibromyalgia.&#xD;
&#xD;
          -  Foreseeable poor compliance with the strategy.&#xD;
&#xD;
          -  Patient with any condition that would prevent participation in the study and&#xD;
             completion of the study procedures, including language limitation.&#xD;
&#xD;
          -  Alcohol and/or drug misuse as determined by the investigator.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Patient is not willing to sign the informed consent.&#xD;
&#xD;
          -  Juridical Protection&#xD;
&#xD;
          -  DAS28&gt;3.2 after one month of a stable dose of prednisone 5 mg/day.&#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>Adeline RUYSSEN-WITRAND, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital of Toulouse, Rheumatology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arnaud CONSTANTIN, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital of Toulouse, Rheumatology Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bordeaux University Hospital</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brest University Hospital</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jean Rougier Hospital</name>
      <address>
        <city>Cahors</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clermont-Ferrand Hospital</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bicêtre Hospital</name>
      <address>
        <city>Le Kremlin-Bicêtre</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lille Hospital</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limoges Hospital</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montpellier Hospital</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pasteur Hospital</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orléans Hospital</name>
      <address>
        <city>Orléans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bichat Hospital</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cochin Hospital</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>La Pitié-Salpétrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lyon Sud Hopsital</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Etienne Hospital</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Strasbourg Hospital</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pierre-Paul Riquet</name>
      <address>
        <city>Toujouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>February 28, 2022</last_update_submitted>
  <last_update_submitted_qc>February 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>low disease activity</keyword>
  <keyword>remission</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Glucocorticoids</mesh_term>
  </intervention_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/NCT02997605
org study id: RC31/15/7824
secondary id: 2016-001618-18
secondary id: PHRC
nct id: NCT02997605
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to compare the proportion of patients who could withdraw from
      prednisone and hydrocortisone one year after a progressive decrease of GC (GC tapering) or a
      hydrocortisone replacement therapy in rheumatoid arthritis in remission or low disease
      activity.
French multicenter double-blind controlled parallel-group randomized clinical trial Phase IV
      assessing whether a hydrocortisone replacement therapy could increase the success rate of GC
      withdrawal at one year, in patients with Rheumatoid Arthritis in low disease activity or
      remission, in comparison to progressive decrease of GC (GC tapering).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: proportion of patients who could withdraw from prednisone and hydrocortisone at one year
time frame: one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement
description: To compare a prednisone tapering strategy to a hydrocortisone replacement strategy on the success rate of prednisone and hydrocortisone withdrawal at one year in Rheumatoid Arthritis patients in low disease activity or remission.
measure: proportion of patients who could withdraw from prednisone
time frame: one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement
description: To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment.
measure: proportion of patients with acute adrenal insufficiency
time frame: one year
description: To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.
measure: proportion of patients with biological adrenal insufficiency
time frame: one year
description: To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.
measure: proportion of patients needing extra prednisone to control flares
time frame: one year
description: To compare the proportion of patients needing extra prednisone to control flares
measure: proportion of patients who have at least one flare confirmed by the investigator during the protocol.
time frame: one year
description: To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol.
measure: area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis)
time frame: one year
description: To compare the area under the curve of the means of the FLARE (Flare Assessment in Rheumatoid Arthritis) at one year with a self-assessment questionnaire.
measure: proportion of patients in DAS28 remission and in DAS28 low disease activity
time frame: 7 and 12 months
description: To compare the proportion of patients in DAS28 remission and in DAS28 low disease activity at 7 and 12 months between the groups.
measure: medians of Health Assessment Questionnaire (HAQ)
time frame: 4, 7 months and 1 year
description: To compare the medians of HAQ at 4, 7 months and one year between the groups.
measure: medians of Rheumatoid Arthritis Impact of Disease (RAID)
time frame: 4, 7 months and 1 year
description: To compare the medians of RAID at 4, 7 months and one year between the groups.
measure: medians of EuroQol 5-dimensional Descriptive system (EQ-5D)
time frame: 4, 7 months and 1 year
description: To compare the medians of EQ-5D at 4, 7 months and one year between the groups.
measure: medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F)
time frame: 4, 7 months and 1 year
description: To compare the medians of FACIT-F at 4, 7 months and one year between the groups.
measure: proportion of patients with Serious Adverse events
time frame: 1 year
description: To compare the proportion of patients with Serious Adverse events at one year between the groups.
arm group label: Glucocorticoid (GC) tapering
arm group type: Active Comparator
description: "GC tapering group": patients will be asked to taper prednisone taken every morning at 8.00 AM by decreasing the daily dose by 1 mg every month as soon as they are in remission or Low Disease Activity (LDA). In addition they will receive a placebo of 20 mg/day of hydrocortisone (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg/day (at 8.00 AM) of hydrocortisone placebo for 3 months before discontinuing the hydrocortisone placebo.
arm group label: Hydrocortisone replacer
arm group type: Active Comparator
description: "Hydrocortisone replacer group": patients will replace prednisone with 20 mg of hydrocortisone on a daily basis (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg daily (at 8.00 AM) for 3 months then stop as soon as they are in remission or LDA, as well as a prednisone placebo (at 8.00 AM) with a schedule to taper the prednisone placebo by 1mg/day every month until discontinuation.
intervention type: Drug
intervention name: GlucoCorticoid
description: After inclusion in the study, the first part is an open follow-up period where all patients will receive 5 mg of prednisone daily for one month. After one month, if patients still have a DAS28 ≤3.2, they will be randomized into two arms: Group 1: "GC tapering group" / Group 2: "Hydrocortisone replacement group".
After randomisation, there are four scheduled visits: M4, M7, M9 and M12. Patients withdrawing from GC therapy will be instructed, that if they start feeling unwell during or after the GC tapering protocol they should not taper the steroid dose any further, but contact the centre responsible for the protocol. If GC induced adrenal insufficiency is confirmed or strongly suspected, GC replacement will be secured using hydrocortisone.
arm group label: Glucocorticoid (GC) tapering
arm group label: Hydrocortisone replacer
other name: Prednisone, Hydrocortisone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adeline RUYSSEN-WITRAND, MD, PhD
role: Study Chair
affiliation: University Hospital of Toulouse, Rheumatology Center
last name: Arnaud CONSTANTIN, MD, PhD
role: Study Chair
affiliation: University Hospital of Toulouse, Rheumatology Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Prednisone
mesh term: Hydrocortisone
mesh term: Glucocorticoids
sharing ipd: No