<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/NCT03267407</url>
  </required_header>
  <id_info>
    <org_study_id>5U01GH000758-03</org_study_id>
    <nct_id>NCT03267407</nct_id>
  </id_info>
  <brief_title>Vietnam Cryptococcal Retention in Care Study - Version 2.1</brief_title>
  <official_title>Vietnam Cryptococcal Retention in Care Study (CRICS) - Version 2.1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Hospital for Tropical Diseases, Hanoi, Vietnam</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Hospital for Tropical Diseases, Hanoi, Vietnam</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter prospective cohort evaluation of the implementation of a cryptococcal&#xD;
      antigen (CrAg) screening program at selected outpatient HIV clinics (OPCs) and network&#xD;
      laboratories in Vietnam.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The project will be implemented in 2 phases; Phase 1: From August 2015 to March 2017&#xD;
      [projected], HIV-infected patients who present for HIV care and undergo CD4 testing will be&#xD;
      reviewed to determine the proportion of newly presenting patients with advanced disease (CD4&#xD;
      ≤100 cells/μL). Reflex CrAg screening will be performed using Lateral Flow Assay (LFA) for&#xD;
      those with CD4≤100 cells/μL, per Vietnam national guidelines.&#xD;
&#xD;
      Patients with CD4≤100 cells/μL who present for antiretroviral treatment (ART) at a study&#xD;
      OPCs-CRICS Sites- will be recruited into the longitudinal study and followed up with&#xD;
      assessments and the collection of routine and supplemental data for 12 months or through&#xD;
      September 2017 (whichever comes sooner). Those who are CrAg-positive, but have no features of&#xD;
      central nervous system (CNS) disease, will be treated with high-dose fluconazole. Those with&#xD;
      symptoms of CNS disease will be treated according to national guidelines. Survival, retention&#xD;
      in care, and other clinical outcomes will be documented for patients who test CrAg-positive&#xD;
      and are treated with fluconazole and those who test CrAg-negative. Data from those tested at&#xD;
      participating labs but not eligible for enrollment in the longitudinal study will contribute&#xD;
      to the estimation of the prevalence of CrAg.&#xD;
&#xD;
      Phase 2: From April 2017 to September 2017, a cost and cost-effectiveness analysis of CrAg&#xD;
      screening will be conducted, a routine screening will be continued at existing sites and&#xD;
      expanded to additional sites (preferentially to hospitals affiliated with Phase 1 OPCs and to&#xD;
      other OPCs whose CD4 testing is conducted at laboratories already conducting CrAg screening&#xD;
      as part of Phase 1). CrAg tests will also be made available to screen all patients with&#xD;
      CD4≤100 cells/μL including those who are treatment-experienced. The test will also be made&#xD;
      available for use among symptomatic patients for diagnostic purposes, including cerebral&#xD;
      spinal fluid (CSF) and blood testing. Investigators will monitor prevalence at each testing&#xD;
      site, but screened patients will not be enrolled in longitudinal follow-up. Phase 2 will last&#xD;
      for at least 6 months based on the availability of funding and fluconazole for those who&#xD;
      screen CrAg positive and the availability/stability of CD4 testing.&#xD;
&#xD;
      [Note that follow up of patients enrolled in Phase 1 will continue during this time period,&#xD;
      but is considered to be part of Phase 1 rather than Phase 2. Also, sites included in Phase 2&#xD;
      may change over time as a result of the instability of CD4 testing (e.g., if participating&#xD;
      laboratories stop conducting CD4 testing, those sites might no longer be included; if&#xD;
      participating laboratories begin CD4 testing for other sites, those sites might be&#xD;
      included).]&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 14, 2015</start_date>
  <completion_date type="Anticipated">March 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of HIV-infected adults who have CD4 count ≤ 100 cells/μL</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The number of HIV-infected adults with CD4 count ≤ 100 cells/μL divided by the total number of HIV-infected patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of CrAg-positivity among HIV-infected patients with CD4 ≤100 cells/μL</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The number of CrAg-positivity divided by the number HIV-infected patients with CD4 ≤100 cells/μL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical outcomes including common causes of mortality for people living with HIV (PLHIV) with CD4 ≤ 100 cells/μL who are enrolled in a programmatic rollout of screening for CrAg</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>Clinical outcomes include HIV-related hospitalization, causes of death, new AIDS defining opportunistic infections at 6 and 12 month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Twelve (12) month all-causes and cryptococcal meningitis (CM)-related mortality among patients who screen CrAg-positive and CrAg-negative</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The 12-month mortality among two groups of HIV-infected patients with CD4 ≤ 100 cells/μL who are enrolled in care and treatment:&#xD;
Those who are CrAg-positive and are treated with high-dose fluconazole;&#xD;
Those who are CrAg-negative.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Twelve (12) month retention among patients who screen CrAg-positive and CrAg-negative</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The 12-month retention in care among two groups of HIV-infected patients with CD4 ≤ 100 cells/μL who are newly enrolled in care and treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Challenges associated with implementation of routine plasma CrAg screening in clinics providing HIV care</measure>
    <time_frame>August 2015 to March 2018</time_frame>
    <description>The challenges associated with implementation may include lost to follow up, incomplete documentation, and poor retention in care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lessons learned with participating sites</measure>
    <time_frame>August 2015 to March 2018</time_frame>
    <description>This will be delivered at reflection and transition workshops with participating sites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total costs and unit cost per person screened, per CrAg+ treated by site, lab facility type, and cost component.</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The costs of implementing CrAg screening based on data to be collected at 22 participating clinics participating in Phase 1 and provider costs associated with CM treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental cost-effectiveness ratio (cost per CM death averted and cost per quality adjusted life year (QALY))</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The incremental cost-effectiveness analysis of CrAg screening compared with a standard of care (no CrAg screening, and treatment for symptomatic CM only).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cost savings and amount of financial resources required to implement CrAg screening</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>Potential cost savings from implementing CrAg screening and financial resources required to implement CrAg screening under different scale-up scenarios and for national rollout</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of stored samples that test positive for TmAg</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The prevalence of Talaromyces marneffei antigenemia (TmAg) in stored CRICS samples using the Mannose phosphate isomerase 1 (MP1) enzyme-linked immunosorbent assay (ELISA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six (6) and twelve (12) month all-causes and Talaromyces marneffei-related mortality among patients who screen TmAg-positive and TmAg-negative</measure>
    <time_frame>August 2015 to March 2017</time_frame>
    <description>The impact of TmAg positivity on mortality</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">1184</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>Cryptococcal Meningitis</condition>
  <condition>Opportunistic Infections, HIV Related</condition>
  <condition>Cryptococcosis</condition>
  <condition>Mycosis; Opportunistic</condition>
  <condition>Mycosis Fungoides</condition>
  <arm_group>
    <arm_group_label>CrAg(+) and CM(-)</arm_group_label>
    <description>(1) Patients with CrAg positive without meningitis results will receive preemptive high-dose fluconazole to prevent developing meningitis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CrAg(+) and CM(+)</arm_group_label>
    <description>(2) Patients with CrAg positive and meningitis results will receive standard treatment for cryptococcal meningitis, following national guidelines.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CrAg(-)</arm_group_label>
    <description>(3) Patients with CrAg negative results will be managed as other HIV infected patients with the standard of care, following national guidelines.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Preemptive high-dose Fluconazole</intervention_name>
    <description>Patients with advanced HIV diseases are screened for Cryptococcal Antigen using LFA CrAg tests. Then patients with CrAg positivity and without meningitis are given preemptive high-dose fluconazole to prevent the development of cryptococcal meningitis, which is one of the leading cause of death among immunocompromized patients.</description>
    <arm_group_label>CrAg(+) and CM(+)</arm_group_label>
    <arm_group_label>CrAg(+) and CM(-)</arm_group_label>
    <arm_group_label>CrAg(-)</arm_group_label>
    <other_name>Preemptive Fluconazole</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with advanced HIV infection (CD4&lt;100 cells/microliters) who are eligible to&#xD;
        inclusion and exclusion criteria are recruited and followed up into the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged ≥ 18 years (having passed 18th birthday using Western calendar)&#xD;
&#xD;
          -  Confirmed HIV infection using National Testing Algorithm&#xD;
&#xD;
          -  CD4 ≤100 cells/μL&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
          -  Enrolled at and plan to receive ongoing outpatient care at one of the selected study&#xD;
             OPCs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of prior CM&#xD;
&#xD;
          -  Receipt of systemic antifungal medication for more than 4 consecutive weeks within the&#xD;
             past 6 months&#xD;
&#xD;
          -  Receipt of ART for more than 4 consecutive weeks within the past year&#xD;
&#xD;
          -  For CrAg-positive patients only: Known to be currently pregnant or planning to become&#xD;
             pregnant during the study period&#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>Kinh V Nguyen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Hospital for Tropical Diseases, Hanoi, Vietnam</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Hospital for Tropical Diseases</name>
      <address>
        <city>Hanoi</city>
        <zip>100000</zip>
        <country>Vietnam</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Vietnam</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>September 10, 2017</last_update_submitted>
  <last_update_submitted_qc>September 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Hospital for Tropical Diseases, Hanoi, Vietnam</investigator_affiliation>
    <investigator_full_name>Vu Quoc Dat</investigator_full_name>
    <investigator_title>Lead Coordinator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Opportunistic Infections</mesh_term>
    <mesh_term>Meningitis, Cryptococcal</mesh_term>
    <mesh_term>Cryptococcosis</mesh_term>
    <mesh_term>AIDS-Related Opportunistic Infections</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
    <mesh_term>Meningitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Please contact principal investigators for any inquiries.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03267407/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03267407/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03267407
org study id: 5U01GH000758-03
nct id: NCT03267407
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a multicenter prospective cohort evaluation of the implementation of a cryptococcal
      antigen (CrAg) screening program at selected outpatient HIV clinics (OPCs) and network
      laboratories in Vietnam.
The project will be implemented in 2 phases; Phase 1: From August 2015 to March 2017
      [projected], HIV-infected patients who present for HIV care and undergo CD4 testing will be
      reviewed to determine the proportion of newly presenting patients with advanced disease (CD4
      ≤100 cells/μL). Reflex CrAg screening will be performed using Lateral Flow Assay (LFA) for
      those with CD4≤100 cells/μL, per Vietnam national guidelines.

      Patients with CD4≤100 cells/μL who present for antiretroviral treatment (ART) at a study
      OPCs-CRICS Sites- will be recruited into the longitudinal study and followed up with
      assessments and the collection of routine and supplemental data for 12 months or through
      September 2017 (whichever comes sooner). Those who are CrAg-positive, but have no features of
      central nervous system (CNS) disease, will be treated with high-dose fluconazole. Those with
      symptoms of CNS disease will be treated according to national guidelines. Survival, retention
      in care, and other clinical outcomes will be documented for patients who test CrAg-positive
      and are treated with fluconazole and those who test CrAg-negative. Data from those tested at
      participating labs but not eligible for enrollment in the longitudinal study will contribute
      to the estimation of the prevalence of CrAg.

      Phase 2: From April 2017 to September 2017, a cost and cost-effectiveness analysis of CrAg
      screening will be conducted, a routine screening will be continued at existing sites and
      expanded to additional sites (preferentially to hospitals affiliated with Phase 1 OPCs and to
      other OPCs whose CD4 testing is conducted at laboratories already conducting CrAg screening
      as part of Phase 1). CrAg tests will also be made available to screen all patients with
      CD4≤100 cells/μL including those who are treatment-experienced. The test will also be made
      available for use among symptomatic patients for diagnostic purposes, including cerebral
      spinal fluid (CSF) and blood testing. Investigators will monitor prevalence at each testing
      site, but screened patients will not be enrolled in longitudinal follow-up. Phase 2 will last
      for at least 6 months based on the availability of funding and fluconazole for those who
      screen CrAg positive and the availability/stability of CD4 testing.

      [Note that follow up of patients enrolled in Phase 1 will continue during this time period,
      but is considered to be part of Phase 1 rather than Phase 2. Also, sites included in Phase 2
      may change over time as a result of the instability of CD4 testing (e.g., if participating
      laboratories stop conducting CD4 testing, those sites might no longer be included; if
      participating laboratories begin CD4 testing for other sites, those sites might be
      included).]
observational model: Cohort
time perspective: Prospective
measure: Proportion of HIV-infected adults who have CD4 count ≤ 100 cells/μL
time frame: August 2015 to March 2017
description: The number of HIV-infected adults with CD4 count ≤ 100 cells/μL divided by the total number of HIV-infected patients.
measure: Prevalence of CrAg-positivity among HIV-infected patients with CD4 ≤100 cells/μL
time frame: August 2015 to March 2017
description: The number of CrAg-positivity divided by the number HIV-infected patients with CD4 ≤100 cells/μL
measure: Clinical outcomes including common causes of mortality for people living with HIV (PLHIV) with CD4 ≤ 100 cells/μL who are enrolled in a programmatic rollout of screening for CrAg
time frame: August 2015 to March 2017
description: Clinical outcomes include HIV-related hospitalization, causes of death, new AIDS defining opportunistic infections at 6 and 12 month.
measure: Twelve (12) month all-causes and cryptococcal meningitis (CM)-related mortality among patients who screen CrAg-positive and CrAg-negative
time frame: August 2015 to March 2017
description: The 12-month mortality among two groups of HIV-infected patients with CD4 ≤ 100 cells/μL who are enrolled in care and treatment:
Those who are CrAg-positive and are treated with high-dose fluconazole;
Those who are CrAg-negative.
measure: Twelve (12) month retention among patients who screen CrAg-positive and CrAg-negative
time frame: August 2015 to March 2017
description: The 12-month retention in care among two groups of HIV-infected patients with CD4 ≤ 100 cells/μL who are newly enrolled in care and treatment.
measure: Challenges associated with implementation of routine plasma CrAg screening in clinics providing HIV care
time frame: August 2015 to March 2018
description: The challenges associated with implementation may include lost to follow up, incomplete documentation, and poor retention in care.
measure: Lessons learned with participating sites
time frame: August 2015 to March 2018
description: This will be delivered at reflection and transition workshops with participating sites.
measure: Total costs and unit cost per person screened, per CrAg+ treated by site, lab facility type, and cost component.
time frame: August 2015 to March 2017
description: The costs of implementing CrAg screening based on data to be collected at 22 participating clinics participating in Phase 1 and provider costs associated with CM treatment.
measure: Incremental cost-effectiveness ratio (cost per CM death averted and cost per quality adjusted life year (QALY))
time frame: August 2015 to March 2017
description: The incremental cost-effectiveness analysis of CrAg screening compared with a standard of care (no CrAg screening, and treatment for symptomatic CM only).
measure: Total cost savings and amount of financial resources required to implement CrAg screening
time frame: August 2015 to March 2017
description: Potential cost savings from implementing CrAg screening and financial resources required to implement CrAg screening under different scale-up scenarios and for national rollout
measure: Proportion of stored samples that test positive for TmAg
time frame: August 2015 to March 2017
description: The prevalence of Talaromyces marneffei antigenemia (TmAg) in stored CRICS samples using the Mannose phosphate isomerase 1 (MP1) enzyme-linked immunosorbent assay (ELISA)
measure: Six (6) and twelve (12) month all-causes and Talaromyces marneffei-related mortality among patients who screen TmAg-positive and TmAg-negative
time frame: August 2015 to March 2017
description: The impact of TmAg positivity on mortality
arm group label: CrAg(+) and CM(-)
description: (1) Patients with CrAg positive without meningitis results will receive preemptive high-dose fluconazole to prevent developing meningitis.
arm group label: CrAg(+) and CM(+)
description: (2) Patients with CrAg positive and meningitis results will receive standard treatment for cryptococcal meningitis, following national guidelines.
arm group label: CrAg(-)
description: (3) Patients with CrAg negative results will be managed as other HIV infected patients with the standard of care, following national guidelines.
intervention type: Other
intervention name: Preemptive high-dose Fluconazole
description: Patients with advanced HIV diseases are screened for Cryptococcal Antigen using LFA CrAg tests. Then patients with CrAg positivity and without meningitis are given preemptive high-dose fluconazole to prevent the development of cryptococcal meningitis, which is one of the leading cause of death among immunocompromized patients.
arm group label: CrAg(+) and CM(+)
arm group label: CrAg(+) and CM(-)
arm group label: CrAg(-)
other name: Preemptive Fluconazole
Whole blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kinh V Nguyen, MD
role: Principal Investigator
affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam
facility: 
country: Vietnam
responsible party type: Principal Investigator
investigator affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam
investigator full name: Vu Quoc Dat
investigator title: Lead Coordinator
mesh term: Mycoses
mesh term: HIV Infections
mesh term: Opportunistic Infections
mesh term: Meningitis, Cryptococcal
mesh term: Cryptococcosis
mesh term: AIDS-Related Opportunistic Infections
mesh term: Mycosis Fungoides
mesh term: Meningitis
mesh term: Fluconazole
sharing ipd: Undecided
ipd description: Please contact principal investigators for any inquiries.
provided document: 
provided document: 