<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/NCT03024281</url>
  </required_header>
  <id_info>
    <org_study_id>201605098RIPA</org_study_id>
    <nct_id>NCT03024281</nct_id>
  </id_info>
  <brief_title>Surveillance of Azole Resistance in Aspergillus Isolates in Taiwan</brief_title>
  <official_title>Surveillance of Azole Resistance in Aspergillus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health Research Institutes, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objectives:&#xD;
&#xD;
        1. To investigate the prevalence of azole resistance in Aspergillus clinical isolates&#xD;
           collected in participating hospitals in Taiwan&#xD;
&#xD;
        2. To investigate the prevalence of azole resistance in Aspergillus environmental isolates&#xD;
           in Taiwan&#xD;
&#xD;
        3. To characterize the molecular mechanisms of azole resistance in Aspergillus isolates in&#xD;
           Taiwan&#xD;
&#xD;
        4. To investigate the clonality of Aspergillus clinical and environmental isolates in&#xD;
           Taiwan&#xD;
&#xD;
        5. To describe the genetic relationships between local resistant strains with global&#xD;
           strains&#xD;
&#xD;
      Secondary objective:&#xD;
&#xD;
        1. To describe the clinical characteristics and treatment outcome of patients with proven&#xD;
           or probable invasive aspergillosis&#xD;
&#xD;
        2. To evaluate the clinical impact of azole resistance in patients with proven or probable&#xD;
           invasive aspergillosis in a case-control study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cumulative evidence described the emergence and geographical expansion of azole-resistant&#xD;
      Aspergillus fumigatus associated with azole treatment failure. Multiple amino acid&#xD;
      substitutions in the cyp51A gene have been described to be associated with azole resistance&#xD;
      that emerges during azole treatment, while a resistance mechanism, TR34/L98H mutation in&#xD;
      cyp51A, has been linked to the agricultural use of azole fungicides in Europe, which have&#xD;
      also been widely used in Taiwan for years. The current prevalence of azole-resistant&#xD;
      Aspergillus isolates and mechanisms of azole resistance in Taiwan is not clear. Considering&#xD;
      the potential of geographic migration of resistant isolates from neighboring countries and&#xD;
      the possibility of emergence of locally revolved resistant strains, this 2-year multi-center&#xD;
      project aims to investigate the prevalence rate of azole resistance in Aspergillus clinical&#xD;
      and environmental isolates, to determine the molecular mechanisms of azole resistance, and to&#xD;
      describe the clinical characteristics and treatment outcome of Aspergillus diseases in&#xD;
      Taiwan. Clinical and environmental Aspergillus isolates will be collected and examined, and&#xD;
      clinical data from patients with Aspergillus diseases or colonization will be retrieved and&#xD;
      analyzed. Through this study the investigators anticipate increase in awareness of prevalence&#xD;
      and impact of azole resistance in patient safety in participating hospitals. In addition, the&#xD;
      investigators may update Taiwan treatment guideline for aspergillosis on the basis of these&#xD;
      evidence and knowledge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2016</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment success</measure>
    <time_frame>6 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of patients with complete response or partial response according to the definition described in &quot;Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. Sep 1 2008;47(5):674-683.&quot;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>6 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>12 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breakthrough mold infections</measure>
    <time_frame>6 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of patients with breakthrough mold infections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breakthrough invasive fungal diseases</measure>
    <time_frame>12 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of patients with breakthrough invasive fungal diseases defined as occurrence of a proven or probable invasive fungal diseases according to EORTC/MSG revised definitions while on systemic antifungal therapy or within 15 days of discontinuation of antifungal use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment success</measure>
    <time_frame>12 weeks after diagnosis of proven or probable invasive aspergillosis</time_frame>
    <description>The proportion of patients with complete response or partial response.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Infection; Aspergillus</condition>
  <eligibility>
    <study_pop>
      <textblock>
        A total of 10 hospitals located in different geographic location of Taiwan will be invited&#xD;
        to participate this project. These hospitals are selected based on three criteria: better&#xD;
        quality of routine microbiology laboratory (not reference laboratory), one or more&#xD;
        physicians or microbiologists who are interested in medical mycology, and geographic&#xD;
        location of the hospitals.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        For primary objectives&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with one or more clinical specimens culture positive of Aspergillus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is not a human pathogen of Aspergillus&#xD;
&#xD;
          -  no clinical data available&#xD;
&#xD;
        For secondary objectives (a case-control study in a 1:4 ratio)&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with proven or probable invasive aspergillosis&#xD;
&#xD;
        Case patients: patients infected by azole-resistant isolates Control patients: patients&#xD;
        infected by azole-susceptible isolates&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>WHO, ICMJE WHO and ICMJE</last_name>
    <role>Study Director</role>
    <affiliation>WHO and ICMJE</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chen Yee-Chun, MD, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>65908</phone_ext>
    <email>yeechunchen@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>ICMJE</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chen Yee-Chun, MD, PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>65908</phone_ext>
      <email>yeechunchen@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 15, 2017</last_update_submitted>
  <last_update_submitted_qc>January 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aspergillus</keyword>
  <keyword>Antifungal susceptibility</keyword>
  <keyword>Azole resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspergillosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03024281
org study id: 201605098RIPA
nct id: NCT03024281
lead sponsor: 
collaborator: 
has dmc: No
Primary objectives:

        1. To investigate the prevalence of azole resistance in Aspergillus clinical isolates
           collected in participating hospitals in Taiwan

        2. To investigate the prevalence of azole resistance in Aspergillus environmental isolates
           in Taiwan

        3. To characterize the molecular mechanisms of azole resistance in Aspergillus isolates in
           Taiwan

        4. To investigate the clonality of Aspergillus clinical and environmental isolates in
           Taiwan

        5. To describe the genetic relationships between local resistant strains with global
           strains

      Secondary objective:

        1. To describe the clinical characteristics and treatment outcome of patients with proven
           or probable invasive aspergillosis

        2. To evaluate the clinical impact of azole resistance in patients with proven or probable
           invasive aspergillosis in a case-control study
Cumulative evidence described the emergence and geographical expansion of azole-resistant
      Aspergillus fumigatus associated with azole treatment failure. Multiple amino acid
      substitutions in the cyp51A gene have been described to be associated with azole resistance
      that emerges during azole treatment, while a resistance mechanism, TR34/L98H mutation in
      cyp51A, has been linked to the agricultural use of azole fungicides in Europe, which have
      also been widely used in Taiwan for years. The current prevalence of azole-resistant
      Aspergillus isolates and mechanisms of azole resistance in Taiwan is not clear. Considering
      the potential of geographic migration of resistant isolates from neighboring countries and
      the possibility of emergence of locally revolved resistant strains, this 2-year multi-center
      project aims to investigate the prevalence rate of azole resistance in Aspergillus clinical
      and environmental isolates, to determine the molecular mechanisms of azole resistance, and to
      describe the clinical characteristics and treatment outcome of Aspergillus diseases in
      Taiwan. Clinical and environmental Aspergillus isolates will be collected and examined, and
      clinical data from patients with Aspergillus diseases or colonization will be retrieved and
      analyzed. Through this study the investigators anticipate increase in awareness of prevalence
      and impact of azole resistance in patient safety in participating hospitals. In addition, the
      investigators may update Taiwan treatment guideline for aspergillosis on the basis of these
      evidence and knowledge.
observational model: Case-Only
time perspective: Retrospective
measure: Treatment success
time frame: 6 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of patients with complete response or partial response according to the definition described in "Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. Sep 1 2008;47(5):674-683."
measure: All-cause mortality
time frame: 6 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.
measure: All-cause mortality
time frame: 12 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.
measure: Breakthrough mold infections
time frame: 6 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of patients with breakthrough mold infections
measure: Breakthrough invasive fungal diseases
time frame: 12 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of patients with breakthrough invasive fungal diseases defined as occurrence of a proven or probable invasive fungal diseases according to EORTC/MSG revised definitions while on systemic antifungal therapy or within 15 days of discontinuation of antifungal use
measure: Treatment success
time frame: 12 weeks after diagnosis of proven or probable invasive aspergillosis
description: The proportion of patients with complete response or partial response.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: WHO, ICMJE WHO and ICMJE
role: Study Director
affiliation: WHO and ICMJE
last name: Chen Yee-Chun, MD, PhD
phone: 886-2-23123456
phone ext: 65908
email: yeechunchen@gmail.com
last name: ICMJE
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Aspergillosis
sharing ipd: Undecided