<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/NCT03265405</url>
  </required_header>
  <id_info>
    <org_study_id>INT/IEC/2017/299</org_study_id>
    <nct_id>NCT03265405</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis</brief_title>
  <acronym>SARCORT</acronym>
  <official_title>Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</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>
      For pulmonary sarcoidosis, the initial dose recommended by the joint statement of the&#xD;
      American Thoracic Society (ATS), European Respiratory Society (ERS), and The World&#xD;
      Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) is 20-40 mg per day.5&#xD;
      The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a&#xD;
      higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more&#xD;
      effective in preventing post-treatment relapse by effective initial suppression of the&#xD;
      granulomatous inflammation and reduction of the disease load. In this study, we compare the&#xD;
      efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone)&#xD;
      glucocorticoids in the treatment of acute sarcoidosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Glucocorticoids are the cornerstone of treatment of sarcoidosis and are used as the&#xD;
      first-line agents in patients requiring immunosuppressive therapy.4 The optimal dose and&#xD;
      duration of glucocorticoids is an unresolved issue. For pulmonary sarcoidosis, the initial&#xD;
      dose recommended by the joint statement of the ATS/ERS/WASOG is 20-40 mg per day.5 The&#xD;
      duration of treatment recommended is at least one year. However, mild disease of recent onset&#xD;
      may respond to a shorter duration of treatment. Further, as most of the toxic effects of&#xD;
      glucocorticoids are cumulative, the dose and duration of steroids need to be kept to a&#xD;
      minimum to balance the benefit and risks of treatment.&#xD;
&#xD;
      Two large studies performed about two decades ago used an initial dose of 30 mg and 20 mg&#xD;
      respectively for treating acute sarcoidosis. While the British Thoracic Society employed&#xD;
      steroid treatment (initial dose 30 mg/day) for one year, in the Finnish study, oral&#xD;
      glucocorticoids (initial dose 20 mg/day) were administered for three months and were followed&#xD;
      by inhaled budesonide.3,6 In a recent Delphi study of experts, 37% and 20% of the experts&#xD;
      used an initial prednisone equivalent dose of 40 mg per day and 20 mg per day regardless of&#xD;
      weight, respectively.7 About 23% used doses of 20 mg, 30 mg, or 40 mg per day depending on&#xD;
      weight. However, consensus was reached that a dose higher than 40 mg per day is not required.&#xD;
      Apart from the initial response to glucocorticoids in symptoms and lung function, the rate of&#xD;
      relapse after cessation of treatment is an important outcome in the management of&#xD;
      sarcoidosis.&#xD;
&#xD;
      The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a&#xD;
      higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more&#xD;
      effective in preventing post-treatment relapse by effective initial suppression of the&#xD;
      granulomatous inflammation and reduction of the disease load. In this study, we compare the&#xD;
      efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone)&#xD;
      glucocorticoids in the treatment of acute sarcoidosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Actual">October 31, 2022</completion_date>
  <primary_completion_date type="Actual">October 7, 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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relapse or treatment failure</measure>
    <time_frame>18 months</time_frame>
    <description>The proportion of subjects with a relapse or treatment failure in the two study groups (initial dose 40 mg/day versus 20 mg/day of prednisone) at the end of 18 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean time to relapse/treatment failure</measure>
    <time_frame>18 months</time_frame>
    <description>The difference between the mean time to relapse/treatment failure in the study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>18 months</time_frame>
    <description>The proportion of subjects with worsening, stabilization, improvement or resolution of the disease in the study groups at the end of 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function early</measure>
    <time_frame>6 months</time_frame>
    <description>The difference in the mean change in forced vital capacity between the study groups at the end of 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative dose of prednisolone</measure>
    <time_frame>18 months</time_frame>
    <description>The difference in the mean cumulative dose of prednisolone between the study groups at the end of 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects</measure>
    <time_frame>18 months</time_frame>
    <description>The adverse effects of treatment (acne, weight gain, hyperglycemia, hypertension, adrenal insufficiency, osteoporosis and any other adverse effects related to prednisolone) between the study groups at the end of 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at treatment completion</measure>
    <time_frame>6 months</time_frame>
    <description>The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at completion of follow-up</measure>
    <time_frame>18 months</time_frame>
    <description>The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at treatment completion</measure>
    <time_frame>6 months</time_frame>
    <description>The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at completion of follow-up</measure>
    <time_frame>18 months</time_frame>
    <description>The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function late</measure>
    <time_frame>18 months</time_frame>
    <description>The difference in the mean change in forced vital capacity between the study groups at the end of18 months</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Sarcoidosis</condition>
  <arm_group>
    <arm_group_label>Low dose prednisolone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>An initial dose of 20 mg/day will be administered for 8 weeks, followed by 15 mg/day for 8 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium dose prednisolone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>An initial dose of 40 mg/day will be administered for 4 weeks, followed by 30 mg/day for 4 weeks, 20 mg/day for 4 weeks, 15 mg/day for 4 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose prednisolone</intervention_name>
    <description>An initial dose of 20 mg/day will be administered for 8 weeks, followed by 15 mg/day for 8 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.</description>
    <arm_group_label>Low dose prednisolone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medium dose prednisolone</intervention_name>
    <description>An initial dose of 40 mg/day will be administered for 4 weeks, followed by 30 mg/day for 4 weeks, 20 mg/day for 4 weeks, 15 mg/day for 4 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.</description>
    <arm_group_label>Medium dose prednisolone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Computed tomography of the chest consistent with a diagnosis of sarcoidosis of the&#xD;
             lung/mediastinal lymph nodes&#xD;
&#xD;
          2. Diagnosis of sarcoidosis made on cytological or histological samples&#xD;
&#xD;
          3. Having significant symptoms requiring immunosuppressive treatment and/or having&#xD;
             reduced lung function (defined as forced vital capacity or forced expiratory volume in&#xD;
             one second (FEV1) less than 80% predicted) or an extrathoracic manifestation of the&#xD;
             disease requiring treatment with low-medium dose glucocorticoids&#xD;
&#xD;
          4. Onset of symptoms within two years of study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating women&#xD;
&#xD;
          2. Subjects having any manifestation requiring high dose steroid treatment (this includes&#xD;
             symptomatic neurosarcoidosis, life threatening cardiac sarcoidosis, vision threatening&#xD;
             posterior uveitis or other forms of vision threatening ocular sarcoidosis)&#xD;
&#xD;
          3. Having absolute contraindication for prednisone in a dose of 40 mg/day (this includes&#xD;
             untreated glaucoma, uncontrolled diabetes mellitus, untreated infections, untreated&#xD;
             severe psychiatric disorders)&#xD;
&#xD;
          4. Unwilling to participate in the study&#xD;
&#xD;
          5. Having received glucocorticoids (prednisolone equivalent &gt;15 mg/day) for more than&#xD;
             three weeks in the preceding two years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Postgraduate Institute of Medical Education and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>January 7, 2023</last_update_submitted>
  <last_update_submitted_qc>January 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Sahajal Dhooria</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>pulmonary sarcoidosis</keyword>
  <keyword>corticosteroids</keyword>
  <keyword>glucocorticoids</keyword>
  <keyword>relapse</keyword>
  <keyword>interstitial lung disease</keyword>
  <keyword>diffuse parenchymal lung disease</keyword>
  <keyword>immunosuppression</keyword>
  <keyword>mediastinal lymphadenopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</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/NCT03265405
org study id: INT/IEC/2017/299
nct id: NCT03265405
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
For pulmonary sarcoidosis, the initial dose recommended by the joint statement of the
      American Thoracic Society (ATS), European Respiratory Society (ERS), and The World
      Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) is 20-40 mg per day.5
      The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a
      higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more
      effective in preventing post-treatment relapse by effective initial suppression of the
      granulomatous inflammation and reduction of the disease load. In this study, we compare the
      efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone)
      glucocorticoids in the treatment of acute sarcoidosis.
Glucocorticoids are the cornerstone of treatment of sarcoidosis and are used as the
      first-line agents in patients requiring immunosuppressive therapy.4 The optimal dose and
      duration of glucocorticoids is an unresolved issue. For pulmonary sarcoidosis, the initial
      dose recommended by the joint statement of the ATS/ERS/WASOG is 20-40 mg per day.5 The
      duration of treatment recommended is at least one year. However, mild disease of recent onset
      may respond to a shorter duration of treatment. Further, as most of the toxic effects of
      glucocorticoids are cumulative, the dose and duration of steroids need to be kept to a
      minimum to balance the benefit and risks of treatment.

      Two large studies performed about two decades ago used an initial dose of 30 mg and 20 mg
      respectively for treating acute sarcoidosis. While the British Thoracic Society employed
      steroid treatment (initial dose 30 mg/day) for one year, in the Finnish study, oral
      glucocorticoids (initial dose 20 mg/day) were administered for three months and were followed
      by inhaled budesonide.3,6 In a recent Delphi study of experts, 37% and 20% of the experts
      used an initial prednisone equivalent dose of 40 mg per day and 20 mg per day regardless of
      weight, respectively.7 About 23% used doses of 20 mg, 30 mg, or 40 mg per day depending on
      weight. However, consensus was reached that a dose higher than 40 mg per day is not required.
      Apart from the initial response to glucocorticoids in symptoms and lung function, the rate of
      relapse after cessation of treatment is an important outcome in the management of
      sarcoidosis.

      The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a
      higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more
      effective in preventing post-treatment relapse by effective initial suppression of the
      granulomatous inflammation and reduction of the disease load. In this study, we compare the
      efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone)
      glucocorticoids in the treatment of acute sarcoidosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relapse or treatment failure
time frame: 18 months
description: The proportion of subjects with a relapse or treatment failure in the two study groups (initial dose 40 mg/day versus 20 mg/day of prednisone) at the end of 18 months
measure: Mean time to relapse/treatment failure
time frame: 18 months
description: The difference between the mean time to relapse/treatment failure in the study groups
measure: Response
time frame: 18 months
description: The proportion of subjects with worsening, stabilization, improvement or resolution of the disease in the study groups at the end of 18 months
measure: Lung function early
time frame: 6 months
description: The difference in the mean change in forced vital capacity between the study groups at the end of 6 months
measure: Cumulative dose of prednisolone
time frame: 18 months
description: The difference in the mean cumulative dose of prednisolone between the study groups at the end of 18 months
measure: Adverse effects
time frame: 18 months
description: The adverse effects of treatment (acne, weight gain, hyperglycemia, hypertension, adrenal insufficiency, osteoporosis and any other adverse effects related to prednisolone) between the study groups at the end of 18 months
measure: Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at treatment completion
time frame: 6 months
description: The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life
measure: Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at completion of follow-up
time frame: 18 months
description: The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life
measure: Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at treatment completion
time frame: 6 months
description: The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue
measure: Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at completion of follow-up
time frame: 18 months
description: The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue
measure: Lung function late
time frame: 18 months
description: The difference in the mean change in forced vital capacity between the study groups at the end of18 months
arm group label: Low dose prednisolone
arm group type: Active Comparator
description: An initial dose of 20 mg/day will be administered for 8 weeks, followed by 15 mg/day for 8 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.
arm group label: Medium dose prednisolone
arm group type: Active Comparator
description: An initial dose of 40 mg/day will be administered for 4 weeks, followed by 30 mg/day for 4 weeks, 20 mg/day for 4 weeks, 15 mg/day for 4 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.
intervention type: Drug
intervention name: Low dose prednisolone
description: An initial dose of 20 mg/day will be administered for 8 weeks, followed by 15 mg/day for 8 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.
arm group label: Low dose prednisolone
intervention type: Drug
intervention name: Medium dose prednisolone
description: An initial dose of 40 mg/day will be administered for 4 weeks, followed by 30 mg/day for 4 weeks, 20 mg/day for 4 weeks, 15 mg/day for 4 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.
arm group label: Medium dose prednisolone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Sahajal Dhooria
investigator title: Assistant Professor
mesh term: Sarcoidosis
mesh term: Prednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone acetate
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate