<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/NCT03290456</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0020</org_study_id>
    <nct_id>NCT03290456</nct_id>
  </id_info>
  <brief_title>Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.</brief_title>
  <acronym>MAINEPSAN</acronym>
  <official_title>A Prospective, Multicentric, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and&#xD;
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood&#xD;
      of disease control and temporary remission. However, most patients have recurrent relapses&#xD;
      that lead to damage and require repeated treatment associated with long-term morbidity and&#xD;
      death.&#xD;
&#xD;
      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and&#xD;
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile .&#xD;
      Although rituximab is becoming the standard of care for maintenance therapy in these&#xD;
      patients, relapse still occurs and the optimal duration of prednisone therapy remains&#xD;
      debated.&#xD;
&#xD;
      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side&#xD;
      effects. On the other hand, most European trials propose late withdrawal (&gt;18 months) given a&#xD;
      lower observed relapse rate on long-term low dose glucocorticoids treatment.&#xD;
&#xD;
      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant&#xD;
      variable explaining the variability between the proportions of ANCA-associated vasculitis&#xD;
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect&#xD;
      because of the absence of dedicated randomized trial. This meta-analysis concluded that&#xD;
      combined longer-term (i.e. &gt;12 months) use of low dose prednisone or nonzero glucocorticoids&#xD;
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12&#xD;
      months).&#xD;
&#xD;
      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was&#xD;
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in&#xD;
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as&#xD;
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to&#xD;
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and&#xD;
      two thirds of the nonsevere relapses occurred when patients were off prednisone.&#xD;
&#xD;
      The trial detailed here is the first prospective trial evaluating the length of&#xD;
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and&#xD;
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood&#xD;
      of disease control and temporary remission. However, most patients have recurrent relapses&#xD;
      that lead to damage and require repeated treatment associated with long-term morbidity and&#xD;
      death.&#xD;
&#xD;
      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and&#xD;
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile.&#xD;
      Although rituximab is becoming the standard of care for maintenance therapy in these&#xD;
      patients, relapse still occurs and the optimal duration of prednisone therapy remains&#xD;
      debated.&#xD;
&#xD;
      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side&#xD;
      effects. On the other hand, most European trials propose late withdrawal (&gt;18 months) given a&#xD;
      lower observed relapse rate on long-term low dose glucocorticoids treatment.&#xD;
&#xD;
      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant&#xD;
      variable explaining the variability between the proportions of ANCA-associated vasculitis&#xD;
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect&#xD;
      because of the absence of dedicated randomized trial. This meta-analysis concluded that&#xD;
      combined longer-term (i.e. &gt;12 months) use of low dose prednisone or nonzero glucocorticoids&#xD;
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12&#xD;
      months).&#xD;
&#xD;
      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was&#xD;
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in&#xD;
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as&#xD;
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to&#xD;
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and&#xD;
      two thirds of the nonsevere relapses occurred when patients were off prednisone.&#xD;
&#xD;
      The trial detailed here is the first prospective trial evaluating the length of&#xD;
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 20, 2019</start_date>
  <completion_date type="Anticipated">June 4, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 4, 2024</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relapse-free survival, relapse being defined as BVAS &gt; 0.</measure>
    <time_frame>from Screening to Month 30.</time_frame>
    <description>rate of relapse-free survival of patients continuing low-dose prednisone treatment until Month 10 VS those who will have prednisone treatment cessation at Month 1, on remission maintenance with Rituximab therapy, after achievement of remission of GPA or MPA, defined as a survival of patients maintaining a BVAS=0 at Month 30, in patient with newly-diagnosed or relapsing GPA or MPA and who will all have received glucocorticoids for 12 months after diagnosis or last flare before inclusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the rate of serious adverse events between Inclusion and Month 30 after randomization</measure>
    <time_frame>from Day 1 to Month 30</time_frame>
    <description>Proportion of patients with at least one adverse event between inclusion and Month 30.&#xD;
Percentage of patients with at least one serious adverse event between inclusion and Month 30, corresponding to any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or congenital anomaly/birth defect or any other adverse event considered &quot;medically significant&quot;.&#xD;
Number of deaths, whatever the cause at Month 30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the rate of predefined severe events related to glucocorticoids between inclusion and Month 30 including osteoporotic fracture and weight gain.</measure>
    <time_frame>From Screening to Month 30</time_frame>
    <description>Percentage of patients with at least one predefined severe event corresponding to adverse events of grade 3 to 5 of the Common Terminology Criteria, including severe side effect related to glucocorticoids (infection requiring hospitalization or intravenous antibiotics, osteoporotic fracture, diabetes requiring medication, cardiovascular event, symptomatic osteonecrosis, psychiatric or mood disorder requiring drug administration, weight gain &gt;10 kg) between inclusion and Month 30&#xD;
- Weight gain between inclusion and Month 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the rate of vasculitis relapse at Month 30</measure>
    <time_frame>from Day 1 to Month 30</time_frame>
    <description>Proportion of patients with minor or major vasculitis relapse between inclusion and Month 30 (BVAS &gt;0) and time to first vasculitis relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the prednisone use between inclusion and Month 30</measure>
    <time_frame>from screening to Month 30</time_frame>
    <description>Prednisone area under the curve of administrated dose between inclusion and Month 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare variation of the Bone mineral density and markers between inclusion and Month 30</measure>
    <time_frame>From Screening to Month 30</time_frame>
    <description>Variation of the Bone mineral density between inclusion and Month 30&#xD;
- Variation of the Bone markers including C-terminal crosslinked telopeptide of type I collagen (CTX) and serum procollagen type 1 amino-terminal propeptide (P1NP) between inclusion and Month 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare sequelae assessed by BVAS (vasculitis activity) at 30 months</measure>
    <time_frame>From Screening to Month 30.</time_frame>
    <description>BVAS (vasculitis activity) at 30 months&#xD;
- Variation of BVAS (Vasculitis activity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare sequelae assessed by the Vasculitis Damage Index (VDI) at 30 months</measure>
    <time_frame>From screening to Month 30.</time_frame>
    <description>Vasculitis Damage Index at 30 months&#xD;
Variation of VDI,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To compare sequelae assessed by Combined Damage Assessment Index (CDA) at 30 months</measure>
    <time_frame>From Screening to Month 30.</time_frame>
    <description>Combined Damage Assessment Index at 30 months&#xD;
Variation of CDA (damage),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To compare functional disability at Month 30 after randomization (Day 1) in both arms</measure>
    <time_frame>From Day 1 to Month 30.</time_frame>
    <description>Variation of HAQ (disability) between inclusion and at Month 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare quality of life at Month 30 after randomization (Day 1) in both arms</measure>
    <time_frame>- From Day 1 to Month 30.</time_frame>
    <description>- Variation of SF-36 (quality of life) between inclusion and at Month 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To compare healthcare resource utilization at Month 30 after randomization (Day 1) in both arms</measure>
    <time_frame>From Day 1 to Month 30.</time_frame>
    <description>- Healthcare resource utilization between inclusion and Month 30 being defined as the percentage of patients being hospitalized at least once except only for rituximab infusions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">146</enrollment>
  <condition>Granulomatosis With Polyangitis</condition>
  <arm_group>
    <arm_group_label>Prednisone 5mg/day extended of 12 additional months</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prednisone 5mg/day will be administered from Day 1 to Month 12</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo 5mg/day extended of 12 additional months</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 5mg/day will be administered from Day 1 to Month 12</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone 5mg/day extended of 12 additional months</intervention_name>
    <description>Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.</description>
    <arm_group_label>Prednisone 5mg/day extended of 12 additional months</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo 5mg/day extended of 12 additionnal months.</intervention_name>
    <description>1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13</description>
    <arm_group_label>Placebo 5mg/day extended of 12 additional months</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of MPA or GPA independently of ANCA status,&#xD;
&#xD;
          -  Patient aged of 18 years or older,&#xD;
&#xD;
          -  Patients with newly-diagnosed disease or relapsing disease at the time of screening,&#xD;
             with an inactive disease defined as a BVAS = 0,&#xD;
&#xD;
          -  Patients receiving maintenance infusion of rituximab 500 mg at 6 and 12 months after&#xD;
             the start of vasculitis induction&#xD;
&#xD;
          -  Patients receiving 5-10 mg/day of prednisone at screening,&#xD;
&#xD;
          -  Patient able to give written informed consent prior to participation in the study.&#xD;
&#xD;
          -  At Inclusion visit day, patient must be between 5 and 10 mg/day prednisone and at&#xD;
             randomization visit day (D1), patient must be at 5 mg/day prednisone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with EGPA, or other vasculitides, defined by the ACR criteria and/or the&#xD;
             Chapel Hill Consensus Conference,&#xD;
&#xD;
          -  Patients with vasculitis with active disease defined as a BVAS &gt;0,&#xD;
&#xD;
          -  Patients with acute infections or chronic active infections (including HIV, HBV or&#xD;
             HCV),&#xD;
&#xD;
          -  Patients with active cancer or recent cancer (&lt;5 years), except basocellular carcinoma&#xD;
             and prostatic cancer of low activity controlled by hormonal treatment,&#xD;
&#xD;
          -  Pregnant women and lactation. Patients with childbearing potential should have&#xD;
             reliable contraception for the all duration of the study,&#xD;
&#xD;
          -  Patients with other uncontrolled diseases, including drug or alcohol abuse, severe&#xD;
             psychiatric diseases, that could interfere with participation in the trial according&#xD;
             to the protocol,&#xD;
&#xD;
          -  Patients included in other investigational therapeutic study within the previous 3&#xD;
             months,&#xD;
&#xD;
          -  Patients suspected not to be observant to the proposed treatments,&#xD;
&#xD;
          -  Patients who have white blood cell count ≤4,000/mm3,&#xD;
&#xD;
          -  Patients who have platelet count ≤100,000/mm3,&#xD;
&#xD;
          -  Patients who have ALT or AST level greater than 3 times the upper limit of normal that&#xD;
             cannot be attributed to underlying MPA-GPA disease,&#xD;
&#xD;
          -  Patients unable to give written informed consent prior to participation in the study.&#xD;
&#xD;
          -  Patients with contraindication to use rituximab,&#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>Jean-Christophe LEGA, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospices Civils de Lyon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Christophe LEGA, Pr</last_name>
    <phone>04.78.86.19.79</phone>
    <email>jean-christophe.lega@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xavier Puéchal, Dr</last_name>
    <phone>01.58.41.32.41</phone>
    <email>xavier.puechal@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Amiens-Hôpital Nord</name>
      <address>
        <city>Amiens</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean SCHMIDT, MD</last_name>
      <phone>3 22 66 82 30</phone>
      <phone_ext>+33</phone_ext>
      <email>jean.schmidt@chu-amiens.fr</email>
    </contact>
    <investigator>
      <last_name>Jean SCHMIDT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian LAVIGNE, MD</last_name>
      <phone>2 41 35 38 24</phone>
      <phone_ext>+33</phone_ext>
      <email>chlavigne@chu-angers.fr</email>
    </contact>
    <investigator>
      <last_name>Christian LAVIGNE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinique Rhône-Durance</name>
      <address>
        <city>Avignon</city>
        <zip>84000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Pierre GOBERT, MD</last_name>
      <phone>4 32 75 30 59</phone>
      <phone_ext>+33</phone_ext>
      <email>pgobert@ch-avignon.fr</email>
    </contact>
    <investigator>
      <last_name>Pierre GOBERT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Jeanne d'Arc</name>
      <address>
        <city>Bar-le-Duc</city>
        <zip>55000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Philippe EVON, MD</last_name>
      <phone>3.29.45.88.03</phone>
      <phone_ext>+33</phone_ext>
      <email>pevon@pssm.fr</email>
    </contact>
    <investigator>
      <last_name>Philippe EVON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <zip>93009</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Robin DHOTE, MD</last_name>
      <phone>1 48 95 58 70</phone>
      <phone_ext>+33</phone_ext>
      <email>robin.dhote@avc.aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Robin DHOTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital La Cavale Blanche</name>
      <address>
        <city>Brest</city>
        <zip>29200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claire DE MOREUIL, MD</last_name>
      <phone>2.98.34.73.36</phone>
      <phone_ext>+33</phone_ext>
      <email>claire.demoreuil@chu-brest.fr</email>
    </contact>
    <investigator>
      <last_name>Claire DE MOREUIL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Louis Pradel</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincent COTTIN, Pr</last_name>
      <phone>4 72 35 70 72</phone>
      <phone_ext>+33</phone_ext>
      <email>vincent.cottin@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Vincent COTTIN, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Caen - Cote de Nacre</name>
      <address>
        <city>Caen</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas MARTIN-SILVA, MD</last_name>
      <phone>2 31 06 57 32</phone>
      <phone_ext>+33</phone_ext>
      <email>martinsilva.n@chu-caen.fr</email>
    </contact>
    <investigator>
      <last_name>Nicolas MARTIN-SILVA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Louis Pasteur</name>
      <address>
        <city>Chartres</city>
        <zip>28018</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Richard DAMADE, MD</last_name>
      <phone>2 37 30 30 30</phone>
      <phone_ext>+33</phone_ext>
      <email>rdamade@ch-chartres.fr</email>
    </contact>
    <investigator>
      <last_name>Richard DAMADE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Estaing</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc RUIVARD, Pr</last_name>
      <phone>4 73 75 00 85</phone>
      <phone_ext>+33</phone_ext>
      <email>mruivard@chu-clermontferrand.fr</email>
    </contact>
    <investigator>
      <last_name>Marc RUIVARD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Gabriel Montpied</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier AUMAITRE, Pr</last_name>
      <phone>4 73 75 14 35</phone>
      <phone_ext>+33</phone_ext>
      <email>oaumaitre@chu-clermontferrand.fr</email>
    </contact>
    <investigator>
      <last_name>Olivier AUMAITRE, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHIC Créteil</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antoine FROISSART, MD</last_name>
      <phone>1 45 17 54 80</phone>
      <phone_ext>+33</phone_ext>
      <email>antoine.froissart@chicreteil.fr</email>
    </contact>
    <investigator>
      <last_name>Antoine FROISSART, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU François Mitterrand</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bernard BONNOTTE, Pr</last_name>
      <phone>3 80 29 34 32</phone>
      <phone_ext>+33</phone_ext>
      <email>bernard.bonnotte@chu-dijon.fr</email>
    </contact>
    <investigator>
      <last_name>Bernard BONNOTTE, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU François Mitterrand</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean-Michel REBIBOU, Pr</last_name>
      <phone>3 80 29 34 34</phone>
      <phone_ext>+33</phone_ext>
      <email>Jean-michel.rebibou@chu-dijon.fr</email>
    </contact>
    <investigator>
      <last_name>Jean-Michel REBIBOU, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Lille - Hôpital Claude Huriez</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Eric HACHULLA, Pr</last_name>
      <phone>3 20 44 92 96</phone>
      <phone_ext>+33</phone_ext>
      <email>e-hachulla@chru-lille.fr</email>
    </contact>
    <investigator>
      <last_name>Eric HACHULLA, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Croix Rousse</name>
      <address>
        <city>Lyon</city>
        <zip>69004</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascal SEVE, Pr</last_name>
      <phone>4 26 73 26 36</phone>
      <phone_ext>+33</phone_ext>
      <email>pascal.seve@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Pascal SEVE, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69137</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arnaud HOT, Pr</last_name>
      <phone>4 72 11 75 68</phone>
      <phone_ext>+33</phone_ext>
      <email>arnaud.hot@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Arnaud HOT, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69137</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laurent JULLIARD, Pr</last_name>
      <phone>4 72 11 02 51</phone>
      <phone_ext>+33</phone_ext>
      <email>laurent.juillard@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Laurent JULLIARD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Conception</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gilles KAPLANSKI, Pr</last_name>
      <phone>4 91 38 35 01</phone>
      <phone_ext>+33</phone_ext>
      <email>Gilles.kaplanski@ap-hm.fr</email>
    </contact>
    <investigator>
      <last_name>Gilles KAPLANSKI, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Conception</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Noémie JOURDE CHICHE, Pr</last_name>
      <phone>4 91 38 30 42</phone>
      <phone_ext>+33</phone_ext>
      <email>Noemie.jourde@ap-hm.fr</email>
    </contact>
    <investigator>
      <last_name>Noémie JOURDE CHICHE, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital La Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicolas SCHLEINITZ, Pr</last_name>
      <phone>4 91 38 87 62</phone>
      <phone_ext>+33</phone_ext>
      <email>nicolas.schleinitz@ap-hm.fr</email>
    </contact>
    <investigator>
      <last_name>Nicolas SCHLEINITZ, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>HP Site Belle Isle</name>
      <address>
        <city>Metz</city>
        <zip>57045</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>François MAURIER, MD</last_name>
      <phone>3 57 84 15 01</phone>
      <phone_ext>+33</phone_ext>
      <email>francois.maurier@hp-metz.fr</email>
    </contact>
    <investigator>
      <last_name>François MAURIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nantes - Hôtel Dieu</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine NEEL, MD</last_name>
      <phone>2 40 08 77 65</phone>
      <phone_ext>+33</phone_ext>
      <email>antoine.neel@chu-nantes.fr</email>
    </contact>
    <investigator>
      <last_name>Antoine NEEL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Nice - Hôpital Pasteur 2</name>
      <address>
        <city>Nice</city>
        <zip>06001</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie TIEULIE, MD</last_name>
      <phone>4 92 03 54 77</phone>
      <phone_ext>+33</phone_ext>
      <email>tieulie.n@chu-nice.fr</email>
    </contact>
    <investigator>
      <last_name>Nathalie TIEULIE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital la Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrice CACOUB, Pr</last_name>
      <phone>1 42 17 80 27</phone>
      <phone_ext>+33</phone_ext>
      <email>patrice.cacoub@psl.aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Patrice CACOUB, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xavier PUECHAL, Pr</last_name>
      <phone>1 58 41 29 71</phone>
      <phone_ext>+33</phone_ext>
      <email>xavier.puechal@aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Xavier PUECHAL, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen G. Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alexandre KARRAS, Pr</last_name>
      <phone>1 56 09 37 60</phone>
      <phone_ext>+33</phone_ext>
      <email>alexandre.karras@egp.aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Alexandre KARRAS, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alfred MAHR, Pr</last_name>
      <phone>1 42 49 97 80</phone>
      <phone_ext>+33</phone_ext>
      <email>alfred.mahr@sls.aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Alfred MAHR, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Haut Lévêque</name>
      <address>
        <city>Pessac</city>
        <zip>33600</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean-François VIALLARD, Pr</last_name>
      <phone>5 57 65 64 83</phone>
      <phone_ext>+33</phone_ext>
      <email>jean-francois.viallard@chu-bordeaux.fr</email>
    </contact>
    <investigator>
      <last_name>Jean-François VIALLARD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69310</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Christophe LEGA, Pr</last_name>
      <phone>04.78.86.19.79</phone>
      <email>jean-christophe.lega@chu-lyon.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CH Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mathilde NOUVIER, Pr</last_name>
      <phone>4 72 67 87 01</phone>
      <phone_ext>+33</phone_ext>
      <email>mathilde.nouvier@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Mathilde NOUVIER, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean Christophe LEGA, Pr</last_name>
      <phone>4.78.86.19.79</phone>
      <phone_ext>+33</phone_ext>
      <email>jean-christophe.lega@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Jean Christophe LEGA, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mathieu PUYADE, MD</last_name>
      <phone>5 49 44 32 76</phone>
      <phone_ext>+33</phone_ext>
      <email>mathieu.puyade@chu-poitiers.fr</email>
    </contact>
    <investigator>
      <last_name>Mathieu PUYADE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Rennes - Hôpital Sud</name>
      <address>
        <city>Rennes</city>
        <zip>35200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas LE GALLOU, MD</last_name>
      <phone>2 99 26 71 28</phone>
      <phone_ext>+33</phone_ext>
      <email>Thomas.LE.GALLOU@chu-rennes.fr</email>
    </contact>
    <investigator>
      <last_name>Thomas LE GALLOU, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Charles Nicolle</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ygal BENHAMOU, MD</last_name>
      <phone>2 32 88 90 14</phone>
      <phone_ext>+33</phone_ext>
      <email>ygal.benhamou@chu-rouen.fr</email>
    </contact>
    <investigator>
      <last_name>Ygal BENHAMOU, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vincent POINDRON, MD</last_name>
      <phone>3 69 55 05 21</phone>
      <phone_ext>+33</phone_ext>
      <email>vincent.poindron@chru-strasbourg.fr</email>
    </contact>
    <investigator>
      <last_name>Vincent POINDRON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Hautepierre</name>
      <address>
        <city>Strasbourg</city>
        <zip>67098</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jacques-Eric GOTTENBERG, Pr</last_name>
      <phone>3 88 12 79 54</phone>
      <phone_ext>+33</phone_ext>
      <email>jacques-eric.gottenberg@chru-strasbourg.fr</email>
    </contact>
    <investigator>
      <last_name>Jacques-Eric GOTTENBERG, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopitaux Universaitaire de Strasbourg Hopitaux</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thierry KRUMMEL, MD</last_name>
      <phone>3 69 55 13 22</phone>
      <phone_ext>+33</phone_ext>
      <email>Thierry.krummel@chru-strasbourg.fr</email>
    </contact>
    <investigator>
      <last_name>Thierry KRUMMEL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Foch</name>
      <address>
        <city>Suresnes</city>
        <zip>92150</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mathieu GROH, MD</last_name>
      <phone>1 46 25 24 16</phone>
      <phone_ext>+33</phone_ext>
      <email>je.kahn@hopital-foch.org</email>
    </contact>
    <investigator>
      <last_name>Mathieu GROH, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elisabeth DIOT, MD</last_name>
      <phone>2 47 47 98 19</phone>
      <phone_ext>+33</phone_ext>
      <email>elisabeth.diot@chu-tours.fr</email>
    </contact>
    <investigator>
      <last_name>Elisabeth DIOT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH de Troyes</name>
      <address>
        <city>Troyes</city>
        <zip>10003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascale CHAUVEAU-JOUVE, MD</last_name>
      <phone>3 25 49 49 49</phone>
      <phone_ext>+33</phone_ext>
      <email>pascale.chauveau-jouve@ch-troyes.fr</email>
    </contact>
    <investigator>
      <last_name>Pascale CHAUVEAU-JOUVE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Valenciennes</name>
      <address>
        <city>Valenciennes</city>
        <zip>59322</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas QUEMENEUR, MD</last_name>
      <phone>3 27 14 30 89</phone>
      <phone_ext>+33</phone_ext>
      <email>quemeneur-t@ch-valenciennes.fr</email>
    </contact>
    <investigator>
      <last_name>Thomas QUEMENEUR, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpitaux de Brabois</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Rolland JAUSSAUD, MD</last_name>
      <phone>3 83 15 40 60</phone>
      <phone_ext>+33</phone_ext>
      <email>r.jaussaud@chru-nancy.fr</email>
    </contact>
    <investigator>
      <last_name>Rolland JAUSSAUD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Bretagne Atlantique</name>
      <address>
        <city>Vannes</city>
        <zip>56017</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascal GODMER, MD</last_name>
      <phone>2 97 01 41 45</phone>
      <phone_ext>+33</phone_ext>
      <email>pascal.godmer@ch-bretagne-atlantique.fr</email>
    </contact>
    <investigator>
      <last_name>Pascal GODMER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH de Verdun</name>
      <address>
        <city>Verdun</city>
        <zip>55100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Assetou DIARRASOUBA, MD</last_name>
      <phone>3 29 83 64 42</phone>
      <phone_ext>+33</phone_ext>
      <email>adiarrassouba@ch-verdun.fr</email>
    </contact>
    <investigator>
      <last_name>Assetou DIARRASOUBA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>November 20, 2019</last_update_submitted>
  <last_update_submitted_qc>November 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vasculitis</keyword>
  <keyword>GPA</keyword>
  <keyword>Granulomatosis with Polyangitis</keyword>
  <keyword>MPA</keyword>
  <keyword>Microscopic Polyangitis</keyword>
  <keyword>Systemic anti-neutrophil cytoplasmic antibodies (ANCA)</keyword>
  <keyword>Prednisone</keyword>
  <keyword>glucocorticoids</keyword>
  <keyword>Remission Maintenance</keyword>
  <keyword>Rituximab</keyword>
  <keyword>Cyclophosphamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vasculitis</mesh_term>
    <mesh_term>Systemic Vasculitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</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/NCT03290456
org study id: 69HCL17_0020
nct id: NCT03290456
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood
      of disease control and temporary remission. However, most patients have recurrent relapses
      that lead to damage and require repeated treatment associated with long-term morbidity and
      death.

      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile .
      Although rituximab is becoming the standard of care for maintenance therapy in these
      patients, relapse still occurs and the optimal duration of prednisone therapy remains
      debated.

      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side
      effects. On the other hand, most European trials propose late withdrawal (>18 months) given a
      lower observed relapse rate on long-term low dose glucocorticoids treatment.

      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant
      variable explaining the variability between the proportions of ANCA-associated vasculitis
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect
      because of the absence of dedicated randomized trial. This meta-analysis concluded that
      combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12
      months).

      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and
      two thirds of the nonsevere relapses occurred when patients were off prednisone.

      The trial detailed here is the first prospective trial evaluating the length of
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood
      of disease control and temporary remission. However, most patients have recurrent relapses
      that lead to damage and require repeated treatment associated with long-term morbidity and
      death.

      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile.
      Although rituximab is becoming the standard of care for maintenance therapy in these
      patients, relapse still occurs and the optimal duration of prednisone therapy remains
      debated.

      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side
      effects. On the other hand, most European trials propose late withdrawal (>18 months) given a
      lower observed relapse rate on long-term low dose glucocorticoids treatment.

      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant
      variable explaining the variability between the proportions of ANCA-associated vasculitis
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect
      because of the absence of dedicated randomized trial. This meta-analysis concluded that
      combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12
      months).

      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and
      two thirds of the nonsevere relapses occurred when patients were off prednisone.

      The trial detailed here is the first prospective trial evaluating the length of
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Relapse-free survival, relapse being defined as BVAS > 0.
time frame: from Screening to Month 30.
description: rate of relapse-free survival of patients continuing low-dose prednisone treatment until Month 10 VS those who will have prednisone treatment cessation at Month 1, on remission maintenance with Rituximab therapy, after achievement of remission of GPA or MPA, defined as a survival of patients maintaining a BVAS=0 at Month 30, in patient with newly-diagnosed or relapsing GPA or MPA and who will all have received glucocorticoids for 12 months after diagnosis or last flare before inclusion.
measure: Compare the rate of serious adverse events between Inclusion and Month 30 after randomization
time frame: from Day 1 to Month 30
description: Proportion of patients with at least one adverse event between inclusion and Month 30.
Percentage of patients with at least one serious adverse event between inclusion and Month 30, corresponding to any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or congenital anomaly/birth defect or any other adverse event considered "medically significant".
Number of deaths, whatever the cause at Month 30.
measure: Compare the rate of predefined severe events related to glucocorticoids between inclusion and Month 30 including osteoporotic fracture and weight gain.
time frame: From Screening to Month 30
description: Percentage of patients with at least one predefined severe event corresponding to adverse events of grade 3 to 5 of the Common Terminology Criteria, including severe side effect related to glucocorticoids (infection requiring hospitalization or intravenous antibiotics, osteoporotic fracture, diabetes requiring medication, cardiovascular event, symptomatic osteonecrosis, psychiatric or mood disorder requiring drug administration, weight gain >10 kg) between inclusion and Month 30
- Weight gain between inclusion and Month 30
measure: To compare the rate of vasculitis relapse at Month 30
time frame: from Day 1 to Month 30
description: Proportion of patients with minor or major vasculitis relapse between inclusion and Month 30 (BVAS >0) and time to first vasculitis relapse
measure: To compare the prednisone use between inclusion and Month 30
time frame: from screening to Month 30
description: Prednisone area under the curve of administrated dose between inclusion and Month 30
measure: To compare variation of the Bone mineral density and markers between inclusion and Month 30
time frame: From Screening to Month 30
description: Variation of the Bone mineral density between inclusion and Month 30
- Variation of the Bone markers including C-terminal crosslinked telopeptide of type I collagen (CTX) and serum procollagen type 1 amino-terminal propeptide (P1NP) between inclusion and Month 30
measure: To compare sequelae assessed by BVAS (vasculitis activity) at 30 months
time frame: From Screening to Month 30.
description: BVAS (vasculitis activity) at 30 months
- Variation of BVAS (Vasculitis activity)
measure: To compare sequelae assessed by the Vasculitis Damage Index (VDI) at 30 months
time frame: From screening to Month 30.
description: Vasculitis Damage Index at 30 months
Variation of VDI,
measure: - To compare sequelae assessed by Combined Damage Assessment Index (CDA) at 30 months
time frame: From Screening to Month 30.
description: Combined Damage Assessment Index at 30 months
Variation of CDA (damage),
measure: - To compare functional disability at Month 30 after randomization (Day 1) in both arms
time frame: From Day 1 to Month 30.
description: Variation of HAQ (disability) between inclusion and at Month 30
measure: To compare quality of life at Month 30 after randomization (Day 1) in both arms
time frame: - From Day 1 to Month 30.
description: - Variation of SF-36 (quality of life) between inclusion and at Month 30
measure: - To compare healthcare resource utilization at Month 30 after randomization (Day 1) in both arms
time frame: From Day 1 to Month 30.
description: - Healthcare resource utilization between inclusion and Month 30 being defined as the percentage of patients being hospitalized at least once except only for rituximab infusions
arm group label: Prednisone 5mg/day extended of 12 additional months
arm group type: Experimental
description: Prednisone 5mg/day will be administered from Day 1 to Month 12
arm group label: Placebo 5mg/day extended of 12 additional months
arm group type: Placebo Comparator
description: Placebo 5mg/day will be administered from Day 1 to Month 12
intervention type: Drug
intervention name: Prednisone 5mg/day extended of 12 additional months
description: Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.
arm group label: Prednisone 5mg/day extended of 12 additional months
intervention type: Drug
intervention name: Placebo 5mg/day extended of 12 additionnal months.
description: 1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13
arm group label: Placebo 5mg/day extended of 12 additional months
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Christophe LEGA, Pr
role: Principal Investigator
affiliation: Hospices Civils de Lyon
last name: Jean-Christophe LEGA, Pr
phone: 04.78.86.19.79
email: jean-christophe.lega@chu-lyon.fr
last name: Xavier Puéchal, Dr
phone: 01.58.41.32.41
email: xavier.puechal@aphp.fr
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country: France
responsible party type: Sponsor
mesh term: Vasculitis
mesh term: Systemic Vasculitis
mesh term: Prednisone
sharing ipd: No