<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/NCT03827278</url>
  </required_header>
  <id_info>
    <org_study_id>TSM-AMB-VOR-2018</org_study_id>
    <nct_id>NCT03827278</nct_id>
  </id_info>
  <brief_title>Comparative Study of Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin Sequential Itraconazole Therapy</brief_title>
  <acronym>CSHHTVASIT</acronym>
  <official_title>Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin B Sequential Itraconazole Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guangxi Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>First Affiliated Hospital of Guangxi Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Second Affiliated Hospital of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fourth People's Hospital of Nanning</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guilin Medical College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nanning Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guangxi Medical University</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>
      Through a multi-center large-sample non-randomized controlled study, the effect of&#xD;
      voriconazole, amphotericin B sequential itraconazole therapy on Talaromyces in Human&#xD;
      Immunodeficiency Virus（HIV）negative hosts were compared to clarify whether the two therapies&#xD;
      were equivalent; A comprehensive efficacy evaluation system and standard treatment program&#xD;
      was established to provide a basis for standardized treatment of Talaromyces in Human&#xD;
      Immunodeficiency Virus negative hosts.The observational indicators included: 2-week all-cause&#xD;
      mortality; 24-week all-cause mortality; clinical improvement time; level of decrease of&#xD;
      fungus in the blood culture medium two weeks before treatment; recurrence; appearance of&#xD;
      adverse drug reaction at the level 3 and above. Dynamically monitor the immune cells and&#xD;
      factors like anti-Interferon-γ autoantibodies, Interferon-γ, Th1/Th2, and Th17/Treg in the&#xD;
      HIV-negative Talaromyces host microenvironment, and observe the host's immune status and its&#xD;
      change. 3. study the effect of absence of Interferon-γ and Interferon-γ Receptor (IFN-γR）on&#xD;
      the activation and function of anti-Interferon-γ autoantibodies, Th1/Th2, and Th17/Treg by&#xD;
      establishing a Talaromyces mouse model that knocks out the Interferon-γ and IFN-γR gene and a&#xD;
      IFN-γ silenced cell model; Study the effect of anti-IFN-γ autoantibody on the activation and&#xD;
      function of IFN-γ、Th1/Th2、Th17/Treg by increasing its titer in vitro and vivo; determine by&#xD;
      which path the anti-IFN-γ autoantibody of HIV-negative host influences its immune regulation&#xD;
      mechanism; finally, the intervention effect of IFN-γ on high titer anti-IFN-γ autoantibodies&#xD;
      is studied, providing a new idea for immunotargeted therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 30, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with all-cause mortality</measure>
    <time_frame>up to 2 weeks</time_frame>
    <description>defined as the absolute risk of death from any cause during the first 2 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with all-cause mortality</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>defined as the absolute risk of death from any cause during 24 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Clinical resolution of talaromyces</measure>
    <time_frame>3 days</time_frame>
    <description>Clinical resolution of talaromyces was defined as a temperature of less than 38°C (100°F) for 3 days, resolution of skin lesions, and tertile blood cultures. Early fungicidal activity was defined as the rate of decline in blood T. marneffei colony forming units (CFUs).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Early fungicidal activity</measure>
    <time_frame>up to 2 weeks</time_frame>
    <description>defined as the rate of decline in blood T. marneffei CFUs from sterical blood cultures obtained during the first 2 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Relapse of talaromyces</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>defined as the recurrence of symptoms and a positive fungal culture from any sterile site that led to reinduction of therapy in patients who had achieved clinical resolution.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Talaromyces in Human Immunodeficiency Virus Negative</condition>
  <condition>To Compare Voriconazole and Amphotericin Sequential Itraconazole Therapy</condition>
  <condition>To Dynamically Monitor the Anti-Interferon-γ Autoantibodies</condition>
  <arm_group>
    <arm_group_label>HIV Negative Host talaromyces using Voriconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Voriconazole On the first day, 6 mg/kg bid was given, and then 4 mg/kg bid was given intravenously for 6 days, and then oral voriconazole 200 mg bid was administered to maintain treatment for at least 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV Negative talaromyces AMB Sequential Itraconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Amphotericin B (AMB) sequential itraconazole group (intravenous amphotericin, dose 0.7 - 1.0 mg / kg / d, 14 days, then changed oral itraconazole 200 mg bid for 10 weeks, after which 100 mg bid maintenance Until cluster of differentiation 4 (CD4+ T) cells are greater than 100 cells/L for at least 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Voriconazole</intervention_name>
    <description>6mg/kg bid, was given on the first day, followed by intravenous 4mg/kg bid for 6 days, followed by oral Valconazole 200mg bid for at least 6 months.&#xD;
Amphotericin B sequential itraconazole group (intravenous amphotericin, dose 0.7 - 1.0 mg / kg / d, 14 days, then changed oral itraconazole 200 mg bid for 10 weeks, after which 100 mg bid maintenance Until CD4+ T cells are greater than 100 cells/L for at least 6 months</description>
    <arm_group_label>HIV Negative Host talaromyces using Voriconazole</arm_group_label>
    <arm_group_label>HIV Negative talaromyces AMB Sequential Itraconazole</arm_group_label>
    <other_name>Amphotericin</other_name>
    <other_name>Itraconazole</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV-negative adults (≥18 years of age) who diagnosis of talaromyces that was confirmed&#xD;
             by either microscopy or culture&#xD;
&#xD;
          2. Must be able to swallow tablets&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy, central nervous system involvement assessed either clinically or by&#xD;
             analyses of cerebrospinal fluid&#xD;
&#xD;
          2. An allergy to voriconazole, itraconazole or amphotericin&#xD;
&#xD;
          3. The concomitant use of certain medications that interact with voriconazole,&#xD;
             itraconazole or amphotericin&#xD;
&#xD;
          4. An alanine aminotransferase or aspartate aminotransferase level of more than 400 U per&#xD;
             liter&#xD;
&#xD;
          5. An absolute neutrophil count of less than 500 per cubic millimeter&#xD;
&#xD;
          6. A creatinine clearance of less than 30 ml per minute (calculated by the method of&#xD;
             Cockcroft and Gault)&#xD;
&#xD;
          7. a concurrent diagnosis of cryptococcal meningitis&#xD;
&#xD;
          8. concurrent treatment with rifampicin&#xD;
&#xD;
          9. previous treatment for talaromyces for more than 48 hours&#xD;
&#xD;
         10. HIV positive who diagnosis of talaromyces.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Guangxi Medical University</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <zip>530021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ye Qiu, M.D</last_name>
      <phone>0771-5356702</phone>
      <email>yeqiu2013graduated@163.com</email>
    </contact>
    <investigator>
      <last_name>Jianquan Zhang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wen Zen, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hui Zhang, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mianluan Pan, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shudan Tang, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yanping Tang, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Haiguang Xu, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jie Huang, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xin Feng, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ye Qiu, M.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Haiting Qin, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Minchao Duan, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/28614691</url>
    <description>Related Info</description>
  </link>
  <results_reference>
    <citation>Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, Cuong DD, Phuc PTH, Vinh VH, Hanh DTH, Tam VV, Thanh NT, Thuy TP, Hang NT, Long HB, Nhan HT, Wertheim HFL, Merson L, Shikuma C, Day JN, Chau NVV, Farrar J, Thwaites G, Wolbers M; IVAP Investigators. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med. 2017 Jun 15;376(24):2329-2340. doi: 10.1056/NEJMoa1613306.</citation>
    <PMID>28614691</PMID>
  </results_reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>February 2, 2019</last_update_submitted>
  <last_update_submitted_qc>February 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guangxi Medical University</investigator_affiliation>
    <investigator_full_name>Qiu Ye</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Talaromyces</keyword>
  <keyword>voriconazole</keyword>
  <keyword>Amphotericin Sequential Itraconazole therapy</keyword>
  <keyword>anti-Interferon-γ autoantibodies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
    <mesh_term>Voriconazole</mesh_term>
    <mesh_term>Amphotericin B</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>http://oldweb.gxmuyfy.cn/gxmufy1/1fy/browse/browse6.asp?id=10080</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03827278
org study id: TSM-AMB-VOR-2018
nct id: NCT03827278
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Through a multi-center large-sample non-randomized controlled study, the effect of
      voriconazole, amphotericin B sequential itraconazole therapy on Talaromyces in Human
      Immunodeficiency Virus（HIV）negative hosts were compared to clarify whether the two therapies
      were equivalent; A comprehensive efficacy evaluation system and standard treatment program
      was established to provide a basis for standardized treatment of Talaromyces in Human
      Immunodeficiency Virus negative hosts.The observational indicators included: 2-week all-cause
      mortality; 24-week all-cause mortality; clinical improvement time; level of decrease of
      fungus in the blood culture medium two weeks before treatment; recurrence; appearance of
      adverse drug reaction at the level 3 and above. Dynamically monitor the immune cells and
      factors like anti-Interferon-γ autoantibodies, Interferon-γ, Th1/Th2, and Th17/Treg in the
      HIV-negative Talaromyces host microenvironment, and observe the host's immune status and its
      change. 3. study the effect of absence of Interferon-γ and Interferon-γ Receptor (IFN-γR）on
      the activation and function of anti-Interferon-γ autoantibodies, Th1/Th2, and Th17/Treg by
      establishing a Talaromyces mouse model that knocks out the Interferon-γ and IFN-γR gene and a
      IFN-γ silenced cell model; Study the effect of anti-IFN-γ autoantibody on the activation and
      function of IFN-γ、Th1/Th2、Th17/Treg by increasing its titer in vitro and vivo; determine by
      which path the anti-IFN-γ autoantibody of HIV-negative host influences its immune regulation
      mechanism; finally, the intervention effect of IFN-γ on high titer anti-IFN-γ autoantibodies
      is studied, providing a new idea for immunotargeted therapy.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with all-cause mortality
time frame: up to 2 weeks
description: defined as the absolute risk of death from any cause during the first 2 weeks
measure: Number of Participants with all-cause mortality
time frame: up to 24 weeks
description: defined as the absolute risk of death from any cause during 24 weeks
measure: Number of Participants with Clinical resolution of talaromyces
time frame: 3 days
description: Clinical resolution of talaromyces was defined as a temperature of less than 38°C (100°F) for 3 days, resolution of skin lesions, and tertile blood cultures. Early fungicidal activity was defined as the rate of decline in blood T. marneffei colony forming units (CFUs).
measure: Number of Participants with Early fungicidal activity
time frame: up to 2 weeks
description: defined as the rate of decline in blood T. marneffei CFUs from sterical blood cultures obtained during the first 2 weeks.
measure: Number of Participants with Relapse of talaromyces
time frame: an average of 1 year
description: defined as the recurrence of symptoms and a positive fungal culture from any sterile site that led to reinduction of therapy in patients who had achieved clinical resolution.
arm group label: HIV Negative Host talaromyces using Voriconazole
arm group type: Experimental
description: Voriconazole On the first day, 6 mg/kg bid was given, and then 4 mg/kg bid was given intravenously for 6 days, and then oral voriconazole 200 mg bid was administered to maintain treatment for at least 6 months.
arm group label: HIV Negative talaromyces AMB Sequential Itraconazole
arm group type: Experimental
description: Amphotericin B (AMB) sequential itraconazole group (intravenous amphotericin, dose 0.7 - 1.0 mg / kg / d, 14 days, then changed oral itraconazole 200 mg bid for 10 weeks, after which 100 mg bid maintenance Until cluster of differentiation 4 (CD4+ T) cells are greater than 100 cells/L for at least 6 months
intervention type: Drug
intervention name: Voriconazole
description: 6mg/kg bid, was given on the first day, followed by intravenous 4mg/kg bid for 6 days, followed by oral Valconazole 200mg bid for at least 6 months.
Amphotericin B sequential itraconazole group (intravenous amphotericin, dose 0.7 - 1.0 mg / kg / d, 14 days, then changed oral itraconazole 200 mg bid for 10 weeks, after which 100 mg bid maintenance Until CD4+ T cells are greater than 100 cells/L for at least 6 months
arm group label: HIV Negative Host talaromyces using Voriconazole
arm group label: HIV Negative talaromyces AMB Sequential Itraconazole
other name: Amphotericin
other name: Itraconazole
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: China
url: https://www.ncbi.nlm.nih.gov/pubmed/28614691
description: Related Info
citation: Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, Cuong DD, Phuc PTH, Vinh VH, Hanh DTH, Tam VV, Thanh NT, Thuy TP, Hang NT, Long HB, Nhan HT, Wertheim HFL, Merson L, Shikuma C, Day JN, Chau NVV, Farrar J, Thwaites G, Wolbers M; IVAP Investigators. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med. 2017 Jun 15;376(24):2329-2340. doi: 10.1056/NEJMoa1613306.
PMID: 28614691
responsible party type: Principal Investigator
investigator affiliation: Guangxi Medical University
investigator full name: Qiu Ye
investigator title: Clinical Professor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Immunologic Deficiency Syndromes
mesh term: Itraconazole
mesh term: Voriconazole
mesh term: Amphotericin B
sharing ipd: Undecided
study doc: 