<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/NCT01715922</url>
  </required_header>
  <id_info>
    <org_study_id>ANRS 12257 Flucocrypto</org_study_id>
    <nct_id>NCT01715922</nct_id>
  </id_info>
  <brief_title>Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa</brief_title>
  <acronym>Flucocrypto</acronym>
  <official_title>Prospective Pilot Study to Evaluate a Standardized Management of Cryptococcal Meningitis in Patients Infected With HIV in Sub-Saharan Africa Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Complemented by Repeat Lumbar Punctures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ANRS, Emerging Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CHU Kamenge, BURUNDI</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Avicenne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Pasteur</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hôpital Necker-Enfants Malades</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut de Médecine et Epidémiologie Appliquée (IMEA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hôpital de Treichville</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hôpital Cocody</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ANRS, Emerging Infectious Diseases</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association&#xD;
      of:&#xD;
&#xD;
        1. Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100&#xD;
           mg/kg/j) as induction therapy&#xD;
&#xD;
        2. lumbar punctures to control intracranial pressure&#xD;
&#xD;
      can decrease mortality rate below 35% at 10 weeks.&#xD;
&#xD;
      This is a non-randomized open label pilot study, with standardized management of&#xD;
      cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients&#xD;
      will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>May 2012</start_date>
  <completion_date type="Anticipated">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>10 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>14 days and 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with negative cerebrospinal fluid (CSF) cultures</measure>
    <time_frame>14 days and 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of relapses of cryptococcal throughout the monitoring period</measure>
    <time_frame>up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of &quot;Immune Reconstitution Inflammatory Syndrome&quot; (IRIS) throughout the monitoring period</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>The IRIS diagnosis criteria will be those given in: Bicanic T, et al. Immune Reconstitution Inflammatory Syndrome in HIV-associated cryptococcal meningitis: a prospective study, J Acquir Immune Defic Syndr 2009; 51:130-134.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and severity of adverse events</measure>
    <time_frame>up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cerebrospinal fluid pressure evolution</measure>
    <time_frame>up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with undetectable viral load</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 count</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of flucytosine in cerebrospinal fluid</measure>
    <time_frame>28 days or 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)</measure>
    <time_frame>at study entry</time_frame>
    <description>on urines, plasma, CSF and whole blood fingerstick</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CSF total volume discharged</measure>
    <time_frame>up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of lumbar punctures performed</measure>
    <time_frame>up to 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of fluconazole in plasma</measure>
    <time_frame>28 days or 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of fluconazole in cerebrospinal fluid</measure>
    <time_frame>28 days or 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of flucytosine in plasma</measure>
    <time_frame>28 days or 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MICs of fluconazole</measure>
    <time_frame>28 days</time_frame>
    <description>MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Cryptococcal Meningitis</condition>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>oral treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Drug: Fluconazole and flucytosine&#xD;
Induction treatment for 2 weeks:&#xD;
Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluconazole</intervention_name>
    <description>Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)</description>
    <arm_group_label>oral treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Flucytosine</intervention_name>
    <description>Flucytosine (100 mg/kg/j) for 2 weeks</description>
    <arm_group_label>oral treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>lumbar punctures</intervention_name>
    <description>lumbar punctures to control intracranial pressure</description>
    <arm_group_label>oral treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 18 years&#xD;
&#xD;
          -  HIV Infection&#xD;
&#xD;
          -  First episode of cryptococcal meningitis on basis CSF India ink and/or CSF&#xD;
             cryptococcal antigen.&#xD;
&#xD;
          -  Glasgow &gt; 9 after lumbar punctures&#xD;
&#xD;
          -  Absence of peripheral focal deficit in the limbs&#xD;
&#xD;
          -  informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemoglobin &lt;7.5 g / dl;&#xD;
&#xD;
          -  neutrophils count &lt;500/mm3;&#xD;
&#xD;
          -  Platelets count &lt;50 000/mm3;&#xD;
&#xD;
          -  transaminases &gt; 5 times upper limit of normal;&#xD;
&#xD;
          -  Troubles with severe mental alertness Glasgow &lt;9 after the initial lumbar puncture;&#xD;
&#xD;
          -  focal neurological deficit in the limbs;&#xD;
&#xD;
          -  Pregnancy or lactation on going;&#xD;
&#xD;
          -  Ongoing systemic antifungal treatment;&#xD;
&#xD;
          -  History of cryptococcal meningitis;&#xD;
&#xD;
          -  Ongoing rifampicin and ritonavir treatment;&#xD;
&#xD;
          -  Subject participating in another study with a risk of mutual interference on the&#xD;
             interpretation of results.&#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>Olivier Bouchaud, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hopital Avicenne, Service des maladies infectieuses, Paris, france</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Théodore Niyangobo, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>CHU Kamenge, Bujumbura, Burundi</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amélie Chabrol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hopital Avicenne, Service des maladies infectieuses, Paris, france</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kakou AKA, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Triechville</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Kamenge</name>
      <address>
        <city>Bujumbura</city>
        <country>Burundi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Prince Régent Charles</name>
      <address>
        <city>Bujumbura</city>
        <country>Burundi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital général</name>
      <address>
        <city>Bururi</city>
        <country>Burundi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital général</name>
      <address>
        <city>Kayanza</city>
        <country>Burundi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital général</name>
      <address>
        <city>Muyinga</city>
        <country>Burundi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Service de Maladies Infectieuses &amp; Tropicales - Hôpital Triechville</name>
      <address>
        <city>Abidjan</city>
        <country>Côte D'Ivoire</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Service de Neurologie - Hôpital Cocody</name>
      <address>
        <city>Abidjan</city>
        <country>Côte D'Ivoire</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Burundi</country>
    <country>Côte D'Ivoire</country>
  </location_countries>
  <link>
    <url>http://www.anrs.fr</url>
    <description>Sponsor web page</description>
  </link>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>July 11, 2016</last_update_submitted>
  <last_update_submitted_qc>July 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cryptococcal meningitis</keyword>
  <keyword>HIV Infections</keyword>
  <keyword>Oral treatment</keyword>
  <keyword>High dose of fluconazole</keyword>
  <keyword>Flucytosine</keyword>
  <keyword>Burundi</keyword>
  <keyword>Ivory Coast</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningitis, Cryptococcal</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>
    <mesh_term>Flucytosine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01715922
org study id: ANRS 12257 Flucocrypto
nct id: NCT01715922
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association
      of:

        1. Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100
           mg/kg/j) as induction therapy

        2. lumbar punctures to control intracranial pressure

      can decrease mortality rate below 35% at 10 weeks.

      This is a non-randomized open label pilot study, with standardized management of
      cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients
      will be enrolled.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mortality rate
time frame: 10 weeks
measure: Mortality rate
time frame: 14 days and 24 weeks
measure: Percentage of patients with negative cerebrospinal fluid (CSF) cultures
time frame: 14 days and 10 weeks
measure: Number of relapses of cryptococcal throughout the monitoring period
time frame: up to 24 weeks
measure: Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period
time frame: up to 24 weeks
description: The IRIS diagnosis criteria will be those given in: Bicanic T, et al. Immune Reconstitution Inflammatory Syndrome in HIV-associated cryptococcal meningitis: a prospective study, J Acquir Immune Defic Syndr 2009; 51:130-134.
measure: Number and severity of adverse events
time frame: up to 24 weeks
measure: Cerebrospinal fluid pressure evolution
time frame: up to 24 weeks
measure: Percentage of patients with undetectable viral load
time frame: 24 weeks
measure: CD4 count
time frame: 24 weeks
measure: Concentration of flucytosine in cerebrospinal fluid
time frame: 28 days or 10 weeks
measure: Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)
time frame: at study entry
description: on urines, plasma, CSF and whole blood fingerstick
measure: CSF total volume discharged
time frame: up to 24 weeks
measure: Number of lumbar punctures performed
time frame: up to 24 weeks
measure: Concentration of fluconazole in plasma
time frame: 28 days or 10 weeks
measure: Concentration of fluconazole in cerebrospinal fluid
time frame: 28 days or 10 weeks
measure: Concentration of flucytosine in plasma
time frame: 28 days or 10 weeks
measure: MICs of fluconazole
time frame: 28 days
description: MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse
arm group label: oral treatment
arm group type: Other
description: Drug: Fluconazole and flucytosine
Induction treatment for 2 weeks:
Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
intervention type: Drug
intervention name: Fluconazole
description: Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
arm group label: oral treatment
intervention type: Drug
intervention name: Flucytosine
description: Flucytosine (100 mg/kg/j) for 2 weeks
arm group label: oral treatment
intervention type: Procedure
intervention name: lumbar punctures
description: lumbar punctures to control intracranial pressure
arm group label: oral treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olivier Bouchaud, PhD
role: Study Chair
affiliation: Hopital Avicenne, Service des maladies infectieuses, Paris, france
last name: Théodore Niyangobo, PhD
role: Study Chair
affiliation: CHU Kamenge, Bujumbura, Burundi
last name: Amélie Chabrol, MD
role: Principal Investigator
affiliation: Hopital Avicenne, Service des maladies infectieuses, Paris, france
last name: Kakou AKA, Professor
role: Principal Investigator
affiliation: CHU Triechville
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Burundi
country: Côte D'Ivoire
url: http://www.anrs.fr
description: Sponsor web page
responsible party type: Sponsor
mesh term: Meningitis, Cryptococcal
mesh term: Meningitis
mesh term: Fluconazole
mesh term: Flucytosine