<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/NCT03026907</url>
  </required_header>
  <id_info>
    <org_study_id>52232</org_study_id>
    <nct_id>NCT03026907</nct_id>
  </id_info>
  <brief_title>Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema</brief_title>
  <acronym>ALIAZ</acronym>
  <official_title>Efficacy of Oral Alitretinoin Versus Oral Azathioprine in Patients With Severe Chronic Non-hyperkeratotic Hand Eczema. A Randomized Prospective Open-label Trial With Blinded Outcome Assessment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy of alitretinoin and azathioprine in the&#xD;
      treatment of patients with severe chronic non-hyperkeratotic hand eczema.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response to treatment/hand eczema severity (Photoguide)</measure>
    <time_frame>24 weeks (end of treatment)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response to treatment/hand eczema severity (Photoguide)</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response to treatment/hand eczema severity (Hand Eczema Severity Index, HECSI)</measure>
    <time_frame>Week 4, 8, 12, 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response</measure>
    <time_frame>Week 4, 8, 12, 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported improvement (Patient Global Assessment, PaGA)</measure>
    <time_frame>Week 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability (adverse events)</measure>
    <time_frame>Up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-utility. QALY's: registered direct/indirect costs, combined with EQ-5D outcome</measure>
    <time_frame>Week 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness: registered direct/indirect costs combined with the primary and secondary effectiveness outcomes (Photoguide/HECSI)</measure>
    <time_frame>Week 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life: questionnaire.</measure>
    <time_frame>Week 12 and 24</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">116</enrollment>
  <condition>Hand Eczema</condition>
  <arm_group>
    <arm_group_label>Alitretinoin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with alitretinoin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Azathioprine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with azathioprine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alitretinoin</intervention_name>
    <description>Oral alitretinoin capsule of 30mg once daily for a total of 24 weeks.</description>
    <arm_group_label>Alitretinoin</arm_group_label>
    <other_name>Toctino</other_name>
    <other_name>9-cis-retinoic acid</other_name>
    <other_name>ATC code: D11AH04</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azathioprine</intervention_name>
    <description>Oral azathioprine tablets twice daily in a dose of 1.5 or 2.5mg/kg/day, depending on the thiopurine methyltransferase (TPMT) activity.</description>
    <arm_group_label>Azathioprine</arm_group_label>
    <other_name>Imuran</other_name>
    <other_name>Azafalk</other_name>
    <other_name>ATC code: L04AX01</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years and ≤ 75 years&#xD;
&#xD;
          -  Severe or very severe chronic non-hyperkeratotic hand eczema for a minimum duration of&#xD;
             3 months as defined by a Physician Global Assessment (PGA) using a validated&#xD;
             Photoguide&#xD;
&#xD;
          -  Refractory to standard therapy, defined as:&#xD;
&#xD;
        Patients received treatment with topical corticosteroids of class II or higher for at least&#xD;
        8 weeks within 3 months before enrolment, with either no response or a transient response.&#xD;
        Patients had also received standard skin care, including emollients and barrier protection&#xD;
        as appropriate, without significant improvement. Patients had avoided irritants and&#xD;
        allergens, if identified, without significant improvement.&#xD;
&#xD;
          -  Women of childbearing potential are required to use at least two forms of&#xD;
             contraception for at least 1 month before starting treatment, during treatment, and&#xD;
             for at least 1 month after finishing treatment; these women are required to take&#xD;
             monthly pregnancy tests&#xD;
&#xD;
          -  Able to provide written Informed Consent&#xD;
&#xD;
          -  Able to speak and read the Dutch language&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General criteria prior to randomization&#xD;
&#xD;
          -  Treatment with alitretinoin or azathioprine in the previous 3 months&#xD;
&#xD;
          -  Hyperkeratotic palmar eczema as defined by the Danish Contact Dermatitis Group&#xD;
&#xD;
          -  Patients with predominantly atopic dermatitis, in which the hands are also involved.&#xD;
             Patients with mild atopic dermatitis, in which the hands are mainly affected are&#xD;
             eligible for inclusion.&#xD;
&#xD;
          -  Psoriasis&#xD;
&#xD;
          -  Active bacterial, fungal, or viral infection of the hands&#xD;
&#xD;
          -  Pregnant/lactating or planning to become pregnant during the study period&#xD;
&#xD;
          -  Treatment with systemic medication or UV radiation within the previous 4 weeks&#xD;
&#xD;
          -  Mentally incompetent&#xD;
&#xD;
          -  Immunocompromised status&#xD;
&#xD;
          -  Known or suspected allergy to ingredients in the study medications&#xD;
&#xD;
          -  Inclusion in a study of an investigational drug within 60 days prior to start of&#xD;
             treatment&#xD;
&#xD;
          -  Current malignancy (other than successfully treated non-metastatic cutaneous squamous&#xD;
             cell or basal cell carcinoma and⁄or localized carcinoma in situ of the cervix)&#xD;
&#xD;
          -  Current active pancreatitis&#xD;
&#xD;
          -  Living vaccine (including bacillus Calmette-Guérin (BCG), varicella, measles, mumps,&#xD;
             rubella, yellow fever, oral polio and oral typhoid) in the last 2 weeks or the planned&#xD;
             application of such a vaccine during the study period&#xD;
&#xD;
          -  Evidence of alcohol abuse or drug addiction&#xD;
&#xD;
          -  Chronic or recurrent infectious diseases&#xD;
&#xD;
          -  Contact sensitizations with clinical relevance to the hands, in which exposure to&#xD;
             allergens is not avoided&#xD;
&#xD;
          -  Hypervitaminosis A due to the use of vitamin A supplements containing &gt;2000 IU&#xD;
&#xD;
          -  Use of drugs with potential to change the effective dosis of study drugs within the&#xD;
             previous 2 weeks&#xD;
&#xD;
        Laboratory exclusion criteria post randomization&#xD;
&#xD;
          -  Alanine aminotransferase (ALAT) and ⁄or aspartate aminotransferase (ASAT) values &gt;&#xD;
             200% of the upper limit of normal&#xD;
&#xD;
          -  Impaired renal function as indicated by a clinically relevant abnormal creatinine&#xD;
             value (to be determined by investigator or treating physician)&#xD;
&#xD;
          -  Anemia as indicated by a clinically relevant lowered hemoglobin value (to be&#xD;
             determined by investigator or treating physician)&#xD;
&#xD;
        Alitretinoin specific&#xD;
&#xD;
          -  Triglycerides &gt; 200% of the upper limit of normal,&#xD;
&#xD;
          -  Cholesterol or low density lipoprotein (LDL) cholesterol values &gt; 200% of the upper&#xD;
             limit of normal&#xD;
&#xD;
          -  Uncontrolled hypothyroidism (to be determined by investigator or treating physician)&#xD;
&#xD;
        Azathioprine specific&#xD;
&#xD;
        • Patients with low or absent thiopurine methyltransferase (TPMT) activity (defined in our&#xD;
        center as &lt;52 nmol/gHb/hour, combined with genotyping showing homozygous of compound&#xD;
        heterozygous mutations) and a subsequent risk for life-threatening myelotoxicity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MLA Schuttelaar, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>MLA Schuttelaar, MD, PhD</last_name>
    <phone>+31503612520</phone>
    <email>m.l.a.schuttelaar@umcg.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>JAF Oosterhaven, MD</last_name>
    <phone>+31503610795</phone>
    <email>j.a.f.oosterhaven@umcg.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9700RB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MLA Schuttelaar, MD, PhD</last_name>
      <phone>+31503612520</phone>
      <email>m.l.a.schuttelaar@umcg.nl</email>
    </contact>
    <contact_backup>
      <last_name>JAF Oosterhaven, MD</last_name>
      <phone>+31503610795</phone>
      <email>j.a.f.oosterhaven@umcg.nl</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>August 18, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>May 1, 2018</last_update_submitted>
  <last_update_submitted_qc>May 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Marie-Louise A Schuttelaar, MD, PhD</investigator_full_name>
    <investigator_title>Principal investigator, dermatologist, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Alitretinoin</keyword>
  <keyword>Azathioprine</keyword>
  <keyword>Hand eczema</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azathioprine</mesh_term>
    <mesh_term>Alitretinoin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data will be published anonymously and will not be possible to trace back to individual participants.</ipd_description>
  </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/NCT03026907
org study id: 52232
nct id: NCT03026907
lead sponsor: 
has dmc: No
The purpose of this study is to compare the efficacy of alitretinoin and azathioprine in the
      treatment of patients with severe chronic non-hyperkeratotic hand eczema.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Response to treatment/hand eczema severity (Photoguide)
time frame: 24 weeks (end of treatment)
measure: Response to treatment/hand eczema severity (Photoguide)
time frame: 12 weeks
measure: Response to treatment/hand eczema severity (Hand Eczema Severity Index, HECSI)
time frame: Week 4, 8, 12, 24
measure: Time to response
time frame: Week 4, 8, 12, 24
measure: Patient reported improvement (Patient Global Assessment, PaGA)
time frame: Week 12 and 24
measure: Safety and tolerability (adverse events)
time frame: Up to 24 weeks
measure: Cost-utility. QALY's: registered direct/indirect costs, combined with EQ-5D outcome
time frame: Week 12 and 24
measure: Cost-effectiveness: registered direct/indirect costs combined with the primary and secondary effectiveness outcomes (Photoguide/HECSI)
time frame: Week 12 and 24
measure: Quality of Life: questionnaire.
time frame: Week 12 and 24
arm group label: Alitretinoin
arm group type: Active Comparator
description: Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with alitretinoin.
arm group label: Azathioprine
arm group type: Active Comparator
description: Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with azathioprine.
intervention type: Drug
intervention name: Alitretinoin
description: Oral alitretinoin capsule of 30mg once daily for a total of 24 weeks.
arm group label: Alitretinoin
other name: Toctino
other name: 9-cis-retinoic acid
other name: ATC code: D11AH04
intervention type: Drug
intervention name: Azathioprine
description: Oral azathioprine tablets twice daily in a dose of 1.5 or 2.5mg/kg/day, depending on the thiopurine methyltransferase (TPMT) activity.
arm group label: Azathioprine
other name: Imuran
other name: Azafalk
other name: ATC code: L04AX01
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: MLA Schuttelaar, MD, PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
last name: MLA Schuttelaar, MD, PhD
phone: +31503612520
email: m.l.a.schuttelaar@umcg.nl
last name: JAF Oosterhaven, MD
phone: +31503610795
email: j.a.f.oosterhaven@umcg.nl
facility: 
status: Recruiting
contact: 
contact backup: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Marie-Louise A Schuttelaar, MD, PhD
investigator title: Principal investigator, dermatologist, MD, PhD
mesh term: Eczema
mesh term: Azathioprine
mesh term: Alitretinoin
sharing ipd: No
ipd description: Data will be published anonymously and will not be possible to trace back to individual participants.