<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/NCT02200146</url>
  </required_header>
  <id_info>
    <org_study_id>HySSAS-FARM639KLZ</org_study_id>
    <nct_id>NCT02200146</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS).</brief_title>
  <acronym>HySSAS</acronym>
  <official_title>Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS). A Multicenter, Prospective, Controlled, Randomized Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milano Bicocca</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Agenzia Italiana del Farmaco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Milano Bicocca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is determining the non-inferiority in the overall success rate and the&#xD;
      safety for a combination therapy with hydroxychloroquine plus low dose glucocorticoids&#xD;
      compared to that for high dose glucocorticoids at 3 and 9 months in patients with pulmonary&#xD;
      sarcoidosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2009</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</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>The primary EFFICACY measure is the per-subject overall success rate at the 3 month visit. Overall response is defined as a combined radiographic and clinical responses.</measure>
    <time_frame>Baseline- After 3 months of treatment</time_frame>
    <description>Subjects is considered clinically cured at the 3 month visit if they will have radiographic success (determined if Chest X-Ray is resolved or improved compared to the baseline; improvement was assessed if there were reduction in hilar adenopathies, less pulmonary involvement, changing in radiographic stage) PLUS a change in at least one of the followings: symptoms (determined by dyspnea or cough index score decrease compared to the baseline), and/or functional improvement (determined by an increase in % of predicted Forced Vital Capacity and/or increase in % of predicted Single-Breath Diffusion capacity of Lung for Carbon monoxide DLCO-SB compared to the baseline), and/or increase in resting Partial pressure of Oxygen in the artery blood (PaO2), and/or worst oxygen saturation increase during 6 Minute Walk Test (6MWT) and/or increase in distance walked at 6MWT, compared to the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The primary SAFETY endpoint is the percent change in lumbar spine (L1-L4) bone mineral density from baseline to month 9 as measured by Dual energy X-ray Absorptiometry (DXA)</measure>
    <time_frame>Baseline - After 9 months of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT)</measure>
    <time_frame>Baseline- After 9 months of therapy</time_frame>
    <description>The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary SAFETY endpoint was the change from baseline in Body Mass Index</measure>
    <time_frame>Baseline - After 3, 6 and 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary SAFETY endpoint was the change from baseline in HbA1c</measure>
    <time_frame>At 3, 6 and 9 months of therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)</measure>
    <time_frame>At 3, 6 and 9 months of therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary SAFETY endpoint was the change from baseline in bone turnover markers and mineral metabolism</measure>
    <time_frame>At months 3 and 9 from the start of therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>Within the 9 months of therapy</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Pulmonary Sarcoidosis</condition>
  <arm_group>
    <arm_group_label>Prednisone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychloroquine + Prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.</description>
    <arm_group_label>Prednisone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine + Prednisone</intervention_name>
    <description>Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.</description>
    <arm_group_label>Hydroxychloroquine + Prednisone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients between 18 and 70 years&#xD;
&#xD;
          -  parenchymal pulmonary involvement at Chest X-Ray (CXR) AND one of the follows:&#xD;
             physiologic abnormalities on pulmonary function testing and/or respiratory symptoms,&#xD;
             and/or exercise-induced abnormalities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to understand protocol and to sign informed consent or not suitable candidate&#xD;
             to comply with the requirements of this study, in the opinion of the investigator&#xD;
&#xD;
          -  Cardiac and neurological sarcoidosis or any other organ involvement&#xD;
&#xD;
          -  End stage lung disease at high-resolution computed tomography (HRCT)&#xD;
&#xD;
          -  Clinical evidence of active infection&#xD;
&#xD;
          -  Documented exposure to beryllium&#xD;
&#xD;
          -  Patients with Forced Expiratory Volume at one second (FEV1) changes after salbutamol&#xD;
             inhalation ≥20%&#xD;
&#xD;
          -  Comorbidity: advanced liver cirrhosis or abnormal liver function, unstable cardiac&#xD;
             disease, moderate to severe renal insufficiency, poorly controlled diabetes&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  A tuberculin skin test (5 I.U.) more than 5 mm&#xD;
&#xD;
          -  Psoriasis&#xD;
&#xD;
          -  Homozygous glucose-6-phosphatase deficiency&#xD;
&#xD;
          -  Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives&#xD;
&#xD;
          -  Visual field changes attributable to 4-aminoquinolines&#xD;
&#xD;
          -  Concomitant therapies: any patient enrolled in the study must be off all prohibited&#xD;
             medications at least 4 weeks before screening. Once patients completed the washout&#xD;
             period, they may enter the screening period that may last up to 30 days&#xD;
&#xD;
          -  Previous therapies: any patient enrolled must be off all medications for sarcoidosis&#xD;
             at least 4 weeks before screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alberto Pesci</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università Milano Bicocca</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Università degli Studi di Milano - Bicocca</name>
      <address>
        <city>Milano</city>
        <zip>20126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>July 24, 2014</last_update_submitted>
  <last_update_submitted_qc>July 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sarcoidosis</keyword>
  <keyword>treatment</keyword>
  <keyword>lung</keyword>
  <keyword>glucocorticoids</keyword>
  <keyword>hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoidosis, Pulmonary</mesh_term>
    <mesh_term>Sarcoidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Prednisone</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/NCT02200146
org study id: HySSAS-FARM639KLZ
nct id: NCT02200146
lead sponsor: 
collaborator: 
has dmc: Yes
The aim of the study is determining the non-inferiority in the overall success rate and the
      safety for a combination therapy with hydroxychloroquine plus low dose glucocorticoids
      compared to that for high dose glucocorticoids at 3 and 9 months in patients with pulmonary
      sarcoidosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The primary EFFICACY measure is the per-subject overall success rate at the 3 month visit. Overall response is defined as a combined radiographic and clinical responses.
time frame: Baseline- After 3 months of treatment
description: Subjects is considered clinically cured at the 3 month visit if they will have radiographic success (determined if Chest X-Ray is resolved or improved compared to the baseline; improvement was assessed if there were reduction in hilar adenopathies, less pulmonary involvement, changing in radiographic stage) PLUS a change in at least one of the followings: symptoms (determined by dyspnea or cough index score decrease compared to the baseline), and/or functional improvement (determined by an increase in % of predicted Forced Vital Capacity and/or increase in % of predicted Single-Breath Diffusion capacity of Lung for Carbon monoxide DLCO-SB compared to the baseline), and/or increase in resting Partial pressure of Oxygen in the artery blood (PaO2), and/or worst oxygen saturation increase during 6 Minute Walk Test (6MWT) and/or increase in distance walked at 6MWT, compared to the baseline
measure: The primary SAFETY endpoint is the percent change in lumbar spine (L1-L4) bone mineral density from baseline to month 9 as measured by Dual energy X-ray Absorptiometry (DXA)
time frame: Baseline - After 9 months of treatment
measure: Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT)
time frame: Baseline- After 9 months of therapy
description: The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months
measure: Secondary SAFETY endpoint was the change from baseline in Body Mass Index
time frame: Baseline - After 3, 6 and 9 months
measure: Secondary SAFETY endpoint was the change from baseline in HbA1c
time frame: At 3, 6 and 9 months of therapy
measure: Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)
time frame: At 3, 6 and 9 months of therapy
measure: Secondary SAFETY endpoint was the change from baseline in bone turnover markers and mineral metabolism
time frame: At months 3 and 9 from the start of therapy
measure: Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events
time frame: Within the 9 months of therapy
arm group label: Prednisone
arm group type: Active Comparator
description: Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.
arm group label: Hydroxychloroquine + Prednisone
arm group type: Experimental
description: Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.
intervention type: Drug
intervention name: Prednisone
description: Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.
arm group label: Prednisone
intervention type: Drug
intervention name: Hydroxychloroquine + Prednisone
description: Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.
arm group label: Hydroxychloroquine + Prednisone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Alberto Pesci
role: Principal Investigator
affiliation: Università Milano Bicocca
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Sarcoidosis, Pulmonary
mesh term: Sarcoidosis
mesh term: Hydroxychloroquine
mesh term: Prednisone