<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/NCT01724268</url>
  </required_header>
  <id_info>
    <org_study_id>11224-12</org_study_id>
    <nct_id>NCT01724268</nct_id>
  </id_info>
  <brief_title>Corticosteroids and Anti TNF in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient</brief_title>
  <official_title>Randomized Controlled Clinical Trial of Low Dose Corticosteroids vs Anti TNF Treatment in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient- a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamad Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamad Medical Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of&#xD;
      adding one of the available anti TNF in the treatment of methotrexate inadequate responder&#xD;
      rheumatoid arthritis patient.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Methotrexate + Prednisolone vs. Methotrexate + anti TNF&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the&#xD;
      joints and of the tissues around the joints, as well as in other organs in the body. Early&#xD;
      diagnosis of rheumatoid arthritis and early aggressive treatment can help prevent joint&#xD;
      damage, deformity and disability.&#xD;
&#xD;
      The management of RA rests on several principles; drug treatment, which comprise disease&#xD;
      modifying anti-rheumatic drugs (DMARDS), but also non-steroidal anti-inflammatory drugs&#xD;
      (NSAIDs) and glucocorticoids (GCs), as well as non-pharmacological measures, such as&#xD;
      physical, occupational and psychological therapeutic approaches, together may lead to&#xD;
      therapeutic success. However, the mainstay of RA treatment is the application of DMARDs.&#xD;
      Methotrexate (MTX) is the anchor drug in the management of RA and has been used for many&#xD;
      decades.&#xD;
&#xD;
      New and highly effective DMARDS have continued to emerge until the most recent years- in&#xD;
      particular, biologic agents which target tumor necrosis factor, the interleukin 1 (IL -1)&#xD;
      receptor, the IL-6 receptor, B lymphocytes and T cell co-stimulation. Furthermore, treatment&#xD;
      strategies have changed during this period, initially by calling for early referral and early&#xD;
      institution of DMARD treatment on the basis of respective evidence of clinical efficacy.&#xD;
&#xD;
      The EULAR (EUROPEAN LEAGUE AGAINST RHEUMATISM) recommendations for treatment of rheumatoid&#xD;
      arthritis (3) emphasize that treatment should be aimed at reaching the target of remission or&#xD;
      low disease activity (DAS 28 score ≤ 3.2) as soon as possible in every patient; as long as&#xD;
      the target has not been reached, treatment should be adjusted by frequent (every 1-3 months)&#xD;
      and strict monitoring.&#xD;
&#xD;
      MTX (1) should be part of the first treatment strategy in patients with active RA and when&#xD;
      MTX contraindications (or intolerance) are present, other DMARDs should be considered.&#xD;
&#xD;
      GCs (1) added at low to moderately high doses to synthetic DMARD monotherapy (or combinations&#xD;
      of synthetic DMARDs) provide benefit as initial short-term treatment, but should be tapered&#xD;
      as rapidly as clinically feasible.&#xD;
&#xD;
      In a systematic review (4), GCs were found to be effective in relieving signs and symptoms&#xD;
      and inhibiting radiographic progression, either as monotherapy or combination therapy.&#xD;
&#xD;
      In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without&#xD;
      GCs, biological DMARDs should be started (1); current practice would be to start a TNF&#xD;
      inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) which should be&#xD;
      combined with MTX.&#xD;
&#xD;
      In most of the studies which included GCs in the management of RA, it was included at the&#xD;
      beginning of the study (1).&#xD;
&#xD;
      In a recent trial (2), Inclusion of low-dose prednisone from the start into a two-year&#xD;
      MTX-based tight control treatment strategy for early RA increases both effectiveness (i.e.&#xD;
      disease activity variables) and outcome (i.e. erosive joint damage) without increasing&#xD;
      toxicity. It also reduces the need for (early) treatment with biologicals.&#xD;
&#xD;
      The anti TNF treatment is expensive and carries the risk of infection. To our knowledge,&#xD;
      there is no study comparing the addition of small doses of steroids of steroids to the&#xD;
      addition of anti TNF in patients who failed or did not tolerate the 25 mg of MTX.&#xD;
&#xD;
      The investigators have designed this study to compare the efficacy of adding small doses of&#xD;
      prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in&#xD;
      patients who did not achieve remission on maximum tolerated MTX dose (up to 25 mg).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2012</start_date>
  <completion_date type="Anticipated">September 2014</completion_date>
  <primary_completion_date type="Anticipated">May 2014</primary_completion_date>
  <phase>Phase 3</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>Disease activity score</measure>
    <time_frame>4 months</time_frame>
    <description>DAS 28: Disease activity score, is a modification of the original DAS score, it divides disease activity into high, moderate, low disease activity, and remission (High disease activity is DAS28 &gt;5.1, moderate is DAS28 of &gt;3.2 to 5.1, low disease activity is DAS28 of 2.6 to 3.2, and remission is DAS28 &lt;2.6).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HAQ Score</measure>
    <time_frame>4 months</time_frame>
    <description>HAQ Score: Health Assessment Questionnaire evaluates patients' ability to perform activities of daily living through their answers to 20 questions designed to assess upper or lower extremity use. These questions are organized into eight categories: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each question is answered on a four-level scale of impairment ranging from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; and 3 = inability to do.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>RHEUMATOID ARTHRITIS</condition>
  <arm_group>
    <arm_group_label>Pred + Meth</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prednisolone : 10 mg daily&#xD;
+ Methotrexate : 25 mg/ day&#xD;
ARM 1 Treatment Arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anti TNF + Meth</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Etanrcept: 50 mg; Adalimumab: 40 mg; Infliximab: 3mg/kg&#xD;
+ Methotrexate 25 mg per day Control Arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pred + Meth</intervention_name>
    <description>PREDNISOLONE 10mg orally ONCE DAILY and Methotrexate 25 mg / day</description>
    <arm_group_label>Pred + Meth</arm_group_label>
    <other_name>Prednisolone</other_name>
    <other_name>Methotrexate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti TNF + Meth</intervention_name>
    <arm_group_label>Anti TNF + Meth</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females aged 18 years or older.&#xD;
&#xD;
          2. Satisfies the 2010 American College of Rheumatology/European League Against Rheumatism&#xD;
             Criteria for Rheumatoid Arthritis.&#xD;
&#xD;
          3. Rheumatoid arthritis of &lt; 2 years duration&#xD;
&#xD;
          4. Has active disease at the time of enrollment. (Modified Disease Activity Score ≥ 3.2)&#xD;
&#xD;
          5. Demonstrates functional status of class I, II, or III as defined by American College&#xD;
             of Rheumatology revised criteria.&#xD;
&#xD;
          6. Is on methotrexate 25 mg weekly or the maximum tolerated dose, therapy should be for&#xD;
             at least 3 months duration and on the highest tolerated dose for the last 4 weeks.&#xD;
&#xD;
          7. Is able and willing to self-inject study drug if assigned to the injectable drug group&#xD;
             or have a designee who can do so.&#xD;
&#xD;
          8. Is PPD negative (skin test for TB exposure) or completed ≥1 month of latent TB&#xD;
             treatment if PPD ≥ 5 or quantiferon (blood test for TB exposure) positive.&#xD;
&#xD;
          9. Is having normal Chest X-Ray.&#xD;
&#xD;
         10. Is Hepatitis B Negative.&#xD;
&#xD;
         11. Not on NSAID (e.g. Ibuprofen) or receiving the same dose of the same NSAID throughout&#xD;
             the study period unless side effects occur&#xD;
&#xD;
         12. All patients in childbearing age should use effective birth control methods&#xD;
&#xD;
         13. Is capable of understanding and signing an informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received any previous treatment with Tumor Necrosis Factor inhibitor or other biologic&#xD;
             treatments for Rheumatoid Arthritis (such as abatacept, rituximab, tocilizumab, or&#xD;
             Anakinra).&#xD;
&#xD;
          2. Received any previous treatment with oral corticosteroids (e.g. prednisolone)&#xD;
&#xD;
          3. Has a known or expected allergy, contraindication, or hypersensitivity to the&#xD;
             medications tested.&#xD;
&#xD;
          4. Any major illness/condition that, in the investigator's judgment, will substantially&#xD;
             increase the risk associated with the subject's participation in, and completion of,&#xD;
             the study, or could preclude the evaluation of the subject's response.&#xD;
&#xD;
          5. Received any of the following within 4 weeks before baseline visit: leflunomide,&#xD;
             hydroxychloroquine, chloroquine, cyclosporine, sulphasalazine, auranofin,&#xD;
             intramuscular gold, azathioprine, minocycline, or D-penicillamine&#xD;
&#xD;
          6. Received cyclophosphamide within 6mths before screening visit.&#xD;
&#xD;
          7. Received any live (attenuated) vaccines within 4 weeks before screening visit.&#xD;
&#xD;
          8. Received intra-articular or subcutaneous corticosteroid injection within 4 weeks&#xD;
             before screening visit.&#xD;
&#xD;
          9. Received bolus intramuscular/ intravenous treatment with corticosteroids (&gt; 20mg&#xD;
             prednisone or equivalent) within 4 weeks before screening visit.&#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>MAGDI H ABDELRAHMAN, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Corporation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>MOHAMMED M HAMMOUDEH, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hamad General Hospital</name>
      <address>
        <city>Doha</city>
        <state>Ad Dawha</state>
        <zip>3050</zip>
        <country>Qatar</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MAGDI H ABDELRAHMAN, MBBS</last_name>
      <email>mrahman1@hmc.org.qa</email>
    </contact>
  </location>
  <location_countries>
    <country>Qatar</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>November 8, 2012</last_update_submitted>
  <last_update_submitted_qc>November 8, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 9, 2012</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>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>Prednisolone</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Methamphetamine</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/NCT01724268
org study id: 11224-12
nct id: NCT01724268
lead sponsor: 
has dmc: Yes
Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of
      adding one of the available anti TNF in the treatment of methotrexate inadequate responder
      rheumatoid arthritis patient.

      Hypothesis:

      Methotrexate + Prednisolone vs. Methotrexate + anti TNF
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the
      joints and of the tissues around the joints, as well as in other organs in the body. Early
      diagnosis of rheumatoid arthritis and early aggressive treatment can help prevent joint
      damage, deformity and disability.

      The management of RA rests on several principles; drug treatment, which comprise disease
      modifying anti-rheumatic drugs (DMARDS), but also non-steroidal anti-inflammatory drugs
      (NSAIDs) and glucocorticoids (GCs), as well as non-pharmacological measures, such as
      physical, occupational and psychological therapeutic approaches, together may lead to
      therapeutic success. However, the mainstay of RA treatment is the application of DMARDs.
      Methotrexate (MTX) is the anchor drug in the management of RA and has been used for many
      decades.

      New and highly effective DMARDS have continued to emerge until the most recent years- in
      particular, biologic agents which target tumor necrosis factor, the interleukin 1 (IL -1)
      receptor, the IL-6 receptor, B lymphocytes and T cell co-stimulation. Furthermore, treatment
      strategies have changed during this period, initially by calling for early referral and early
      institution of DMARD treatment on the basis of respective evidence of clinical efficacy.

      The EULAR (EUROPEAN LEAGUE AGAINST RHEUMATISM) recommendations for treatment of rheumatoid
      arthritis (3) emphasize that treatment should be aimed at reaching the target of remission or
      low disease activity (DAS 28 score ≤ 3.2) as soon as possible in every patient; as long as
      the target has not been reached, treatment should be adjusted by frequent (every 1-3 months)
      and strict monitoring.

      MTX (1) should be part of the first treatment strategy in patients with active RA and when
      MTX contraindications (or intolerance) are present, other DMARDs should be considered.

      GCs (1) added at low to moderately high doses to synthetic DMARD monotherapy (or combinations
      of synthetic DMARDs) provide benefit as initial short-term treatment, but should be tapered
      as rapidly as clinically feasible.

      In a systematic review (4), GCs were found to be effective in relieving signs and symptoms
      and inhibiting radiographic progression, either as monotherapy or combination therapy.

      In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without
      GCs, biological DMARDs should be started (1); current practice would be to start a TNF
      inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) which should be
      combined with MTX.

      In most of the studies which included GCs in the management of RA, it was included at the
      beginning of the study (1).

      In a recent trial (2), Inclusion of low-dose prednisone from the start into a two-year
      MTX-based tight control treatment strategy for early RA increases both effectiveness (i.e.
      disease activity variables) and outcome (i.e. erosive joint damage) without increasing
      toxicity. It also reduces the need for (early) treatment with biologicals.

      The anti TNF treatment is expensive and carries the risk of infection. To our knowledge,
      there is no study comparing the addition of small doses of steroids of steroids to the
      addition of anti TNF in patients who failed or did not tolerate the 25 mg of MTX.

      The investigators have designed this study to compare the efficacy of adding small doses of
      prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in
      patients who did not achieve remission on maximum tolerated MTX dose (up to 25 mg).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease activity score
time frame: 4 months
description: DAS 28: Disease activity score, is a modification of the original DAS score, it divides disease activity into high, moderate, low disease activity, and remission (High disease activity is DAS28 >5.1, moderate is DAS28 of >3.2 to 5.1, low disease activity is DAS28 of 2.6 to 3.2, and remission is DAS28 <2.6).
measure: HAQ Score
time frame: 4 months
description: HAQ Score: Health Assessment Questionnaire evaluates patients' ability to perform activities of daily living through their answers to 20 questions designed to assess upper or lower extremity use. These questions are organized into eight categories: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each question is answered on a four-level scale of impairment ranging from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; and 3 = inability to do.
arm group label: Pred + Meth
arm group type: Experimental
description: Prednisolone : 10 mg daily
+ Methotrexate : 25 mg/ day
ARM 1 Treatment Arm
arm group label: Anti TNF + Meth
arm group type: Active Comparator
description: Etanrcept: 50 mg; Adalimumab: 40 mg; Infliximab: 3mg/kg
+ Methotrexate 25 mg per day Control Arm
intervention type: Drug
intervention name: Pred + Meth
description: PREDNISOLONE 10mg orally ONCE DAILY and Methotrexate 25 mg / day
arm group label: Pred + Meth
other name: Prednisolone
other name: Methotrexate
intervention type: Drug
intervention name: Anti TNF + Meth
arm group label: Anti TNF + Meth
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MAGDI H ABDELRAHMAN, MBBS
role: Principal Investigator
affiliation: Hamad Medical Corporation
last name: MOHAMMED M HAMMOUDEH, MD
role: Principal Investigator
affiliation: Hamad Medical Corporation
facility: 
status: Recruiting
contact: 
country: Qatar
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Prednisolone
mesh term: Methotrexate
mesh term: Methamphetamine